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t29 | t29_7 | yes | People with non‐transfusion dependent beta thalassaemia have higher levels of foetal haemoglobin (the main form of haemoglobin found during the development of a baby before birth). | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_8 | yes | After birth, foetal haemoglobin gradually disappears and is replaced by the defective adult haemoglobin. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_9 | yes | A small amount of foetal haemoglobin remains after birth and is often present in people with non‐transfusion dependent beta thalassaemia. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_10 | no | The higher the level of foetal haemoglobin the less transfusion could be needed. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_11 | yes | Hydroxyurea is an anti‐cancer treatment which increases the level of foetal haemoglobin. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_12 | yes | Therefore, it might reduce the need for blood transfusion in people with non‐transfusion dependent beta thalassaemia. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_13 | yes | However, it is not known whether hydroxyurea is effective and safe and if so, which is the best dose and at which age treatment should start. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_14 | yes | We did not find any randomised controlled trials (where people taking part in the trial have equal chances of being in the treatment or the control group) comparing hydroxyurea with a placebo (a dummy drug) or usual care. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_15 | no | However, we found one randomised controlled trial comparing two different doses of hydroxyurea (10 mg/kg/day versus 20 mg/kg/day given for 24 weeks) and included it in this review. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_16 | no | A total of 61 people took part in this trial. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_17 | no | The lower dose of hydroxyurea appeared to increase levels of foetal haemoglobin, but the higher dose did not. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_18 | yes | We found some evidence that the higher dose was harmful, particularly to the bone marrow. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_19 | no | The trial did not look at whether blood transfusions could be given less often or whether the effects of the anaemia were reduced. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t29 | t29_20 | yes | In the short term, the lower dose does not appear to have any side effects. | Non‐transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non‐transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. Objectives To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non‐transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 30 April 2016. Selection criteria Randomised or quasi‐randomised controlled trials of hydroxyurea in people with non‐transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference ‐2.39 (95% confidence interval ‐ 2.8 to ‐1.98) and mean difference ‐1.5 (95% confidence interval ‐1.83 to ‐1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well‐designed randomised controlled trials with sufficient duration of follow up are recommended. |
t30 | t30_1 | no | We reviewed the evidence for the effect of omalizumab on people with asthma when compared with placebo. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_2 | yes | We focused on whether omalizumab is a beneficial but safe treatment for adults and children with asthma. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_3 | no | Asthma is a respiratory condition that affects millions of people worldwide. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_4 | yes | It is thought that allergy may be an important part of the disease for many people with asthma. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_5 | yes | Omalizumab is a drug that targets a protein, called IgE, and removes it from free circulation in the body. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_6 | yes | IgE is centrally involved in allergy. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_7 | yes | Omalizumab is an expensive drug that is usually given by injection under the skin every two to four weeks. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_8 | no | It is licenced for use in asthma sufferers who are not being adequately treated with standard therapy and who require frequent courses or continuous use of oral steroid tablets. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_9 | no | We looked for evidence on whether administration of omalizumab is better or worse than giving placebo. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_10 | no | Twenty‐five studies, involving 6382 people, were included in this review. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_11 | yes | These studies lasted between eight and 60 weeks. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_12 | no | All of the people included in the studies had asthma, of different severity. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_13 | yes | Both men and women were included, and some of the studies included children and young people. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_14 | yes | All studies compared omalizumab versus placebo. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_15 | yes | In keeping with current medical practice, most studies (21 of 25) used omalizumab given by injection under the skin. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_16 | no | Some of the older studies used omalizumab injected into a vein or given by inhalation. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_17 | yes | Most of the studies were sponsored by the pharmaceutical industry. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_18 | no | We found that people receiving omalizumab were less likely to have a flare‐up (‘exacerbation’) of their asthma. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_19 | no | For example, on average, 26 of 100 people who were receiving placebo (over a 16 to 60‐week period) had an exacerbation compared with an average of 16 of 100 people receiving omalizumab. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_20 | no | People receiving omalizumab were also more likely to be able to reduce the doses of inhaled steroids. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_21 | yes | For example, on average, 21 of 100 people with moderate or severe asthma who were receiving placebo were able to completely stop their inhaled steroids (over a 28 to 32‐week period) compared with an average of 40 of 100 receiving omalizumab. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_22 | no | People receiving omalizumab also experienced improvement in their asthma symptoms and in their health‐related quality of life. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_23 | yes | People receiving omalizumab were no more or less likely to have unwanted side effects overall. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_24 | no | However, people receiving omalizumab were more likely to have skin reactions at the site of the injection. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_25 | yes | Perhaps unfortunately, many of the trials in this review included participants with moderate asthma, and this drug is not licenced for this group. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t30 | t30_26 | yes | More trials need to focus on whether this drug is effective in people with the most severe asthma; evidence for efficacy in this group is poor, in spite of current guidelines. | Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti‐IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add‐on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE‐mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti‐IgE administered in any manner for any duration. Trials with co‐interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti‐IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab‐treated participants compared with those given placebo (weighted mean difference (WMD) ‐118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI ‐154 to ‐84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta 2 ‐agonist medication compared with placebo (mean difference (MD) ‐0.39 puffs per day, 95% CI ‐0.55 to ‐0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD ‐0.58, 95% CI ‐0.84 to ‐0.31) and severe (MD ‐0.30, 95% CI ‐0.49 to ‐0.10) asthma subgroups on a therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double‐dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone‐sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. |
t31 | t31_1 | no | Stroke is a major cause of disability. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_2 | yes | Stroke‐related disability can include difficulty with daily tasks such as toileting, washing, and walking. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_3 | yes | Sometimes disability is so severe that a person becomes dependent on others for performing basic activities (this is known as 'dependence'). | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_4 | yes | Our previous Cochrane Review published in 2012 suggested that SSRI drugs (a class of drug usually used to treat mood problems, which work by changing the level of chemicals in the brain), might improve recovery after stroke, thereby reducing disability and increasing the chance of being independent after a stroke, However, when we looked at only the high‐quality trials, the effect was less convincing. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_5 | yes | A large trial recruiting more than 3000 participants has now been completed and so it is necessary to update this review. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_6 | yes | In our main analyses we decided to include only high‐quality trials, that is those which used rigorous methods to avoid biases (such as the person assessing outcome being aware of whether the stroke survivor received the active drug or placebo). | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_7 | no | In this review, we refer to them as 'low risk of bias' trials. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_8 | yes | If disability and dependency can be improved by a simple drug, this could have a major impact on quality of life for many stroke survivors. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_9 | yes | We also wanted to find out whether SSRIs had other benefits, for example improving the severity of any arm or leg weakness, mood, anxiety, quality of life, and also whether SSRIs were associated with side effects such as bleeding or seizures. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_10 | no | In total we found 63 trials recruiting 9168 stroke survivors within one year of their stroke. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_11 | no | There was a wide age range. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_12 | no | About half the trials required participants to have depression to enter the trial. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_13 | no | The duration, drug, and dose varied between trials. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_14 | no | However, only three of these trials were at low risk of bias; the participants in these trials did not have to be depressed to enter the trial, and they were all recruited soon after the stroke. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_15 | no | When we combined data from these three studies at low risk of bias, which recruited 3249 participants, SSRIs did not affect disability score or dependency. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t31 | t31_16 | yes | SSRIs reduced the risk of future depression but increased the risk of problems with the digestive system. | Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. Objectives To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. Search methods For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). Data collection and analysis We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow‐up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta‐analysis of these three trials found little or no effect of SSRI on either disability score: SMD −0.01 (95% CI −0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate‐quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate‐quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate‐quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate‐quality evidence), with no evidence of heterogeneity (I 2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta‐analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta‐analysis of large ongoing trials will be required to determine the generalisability of these findings. |
t32 | t32_1 | yes | The veins of the leg are designed to return blood from the leg upwards towards the heart. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_2 | yes | Blood is under the force of gravity and, left to itself, would flow downwards. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_3 | yes | Valves within the veins normally prevent blood from flowing downwards (i.e. backwards), however, if these valves become leaky, pressure within the veins increases. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_4 | yes | This high pressure causes swelling, thickening and damage to skin, which may break down to form ulcers. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_5 | yes | Venous leg ulcers are associated with pain and mobility restrictions that affect quality of life. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_6 | yes | Compression of legs with bandages or medical stockings helps to move the blood upwards, and reduces pressure in the veins and tissues. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_7 | no | This treatment has been shown to improve ulcer healing. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_8 | yes | Compression is unpopular because it can be uncomfortable, and only provides a benefit while the bandages or hosiery are worn. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_9 | yes | Even with compression treatment, healing of venous ulcers may still take a long time, and ulcers often come back. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_10 | yes | Traditionally, surgery for venous disease involves removing the veins from the leg. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_11 | yes | The blood is then diverted through the remaining healthy veins. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_12 | yes | This reduces the pressure in the veins and helps prevent ulcers that have healed from coming back. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_13 | yes | Generally, this surgery is performed under a general anaesthetic and involves a period of recovery. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_14 | yes | Some people, particularly the elderly, are less suitable for general anaesthetic and may be at risk of age‐related complications or a prolonged and difficult recovery. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_15 | yes | Newer 'keyhole' surgical techniques destroy the veins with heat, and require only local anaesthesia. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_16 | yes | These treatments have been shown to be as effective as surgery in the treatment of varicose veins in the absence of ulcers, and result in less pain than traditional surgery. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_17 | yes | Since a general anaesthetic can be avoided, there is also a reduced risk associated with the anaesthetic procedure, and the recovery period is shorter. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_18 | yes | The purpose of this review was to compare the effectiveness of these new, minimally invasive surgical techniques with compression therapy for the management of venous leg ulcers. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t32 | t32_19 | yes | We wanted to see how well the different treatments work in terms of ulcer healing and recurrence rates. | Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally‐invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long‐term patient concordance with compression is relatively poor, it may prove more popular, effective and cost‐effective to provide a single intervention to reduce recurrence, rather than life‐long treatment with compression. Objectives To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. Search methods In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library ); Ovid MEDLINE; Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. Selection criteria Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer‐free days. Secondary outcomes sought included patient‐reported quality of life, economic data and adverse events. Data collection and analysis Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately‐powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost‐effectiveness. |
t33 | t33_1 | yes | Clostridium difficile ( C. difficile ) is a bacterium that can live harmlessly in the colon, but when an individual takes an antibiotic for another condition, the C. difficile can grow and replace most of the normal bacterial flora that live in the colon. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_2 | yes | This overgrowth causes C. difficile ‐associated diarrhoea (also known as C. difficile infection ‐ CDI). | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_3 | yes | The symptoms of CDI include diarrhoea, fever and pain. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_4 | yes | CDI may be only mild but in many cases is very serious and, if untreated, can be fatal. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_5 | yes | There are many proposed treatments for CDI, but the most common are withdrawing the antibiotic that caused the CDI and prescribing an antibiotic that kills the bacterium. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_6 | yes | Many antibiotics have been tested in clinical trials for effectiveness and this review studies the comparisons of these antibiotics. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_7 | no | This review is an update of a previously published Cochrane review. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_8 | no | Methods We searched the medical literature up to 26 January 2017. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_9 | yes | All randomised trials that compare two different antibiotics, or variations in dosing of a single antibiotic for treatment of CDI were included. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_10 | yes | Trials comparing antibiotic to placebo (e.g. a sugar pill) or no treatment were sought but, save for one poor quality placebo‐controlled trial, none were found. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_11 | yes | Trials that compared antibiotics to a non‐antibiotic treatment were not included. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_12 | no | Results Twenty‐two studies (total 3215 participants) were included. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_13 | no | The majority of studies enrolled participants with mild to moderate CDI who could tolerate oral antibiotics. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_14 | no | Sixteen of the included studies excluded participants with severe CDI and few participants with severe CDI were included in the other studies. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_15 | no | Twelve different antibiotics were assessed. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_16 | yes | Most of the studies compared vancomycin or metronidazole with other antibiotics. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_17 | no | One small study compared vancomycin to placebo (e.g. sugar pill). | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_18 | no | There were no other studies that compared antibiotic treatment to a placebo or a no treatment control group. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_19 | no | Seventeen of the 22 included studies had quality issues. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_20 | no | In four studies, vancomycin was found to be superior to metronidazole for achieving sustained symptomatic cure (defined as resolution of diarrhoea and no recurrence of CDI). | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_21 | no | A new antibiotic, fidaxomicin, was, in two large studies, found to be superior to vancomycin. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_22 | no | It should be noted that the differences in effectiveness between these antibiotics were not too great and that metronidazole is far less expensive than either vancomycin and fidaxomicin. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_23 | yes | A pooled analysis of two small studies suggests that teicoplanin may be more effective than vancomycin for achieving symptomatic cure. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_24 | yes | The quality of the evidence for the other seven antibiotics in this review was very poor because the studies were very small, and many patients dropped out of these studies before completion. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
t33 | t33_25 | no | One hundred and forty deaths were reported in the studies, all of which were attributed to participants preexisting health problems. | Clostridium difficile ( C. difficile ) is recognized as a frequent cause of antibiotic‐associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. Objectives The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile‐ associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Selection criteria Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Data collection and analysis Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed‐effect model, except where significant heterogeneity was detected, at which time a random‐effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty‐two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy‐two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy‐one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly‐seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo‐controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co‐morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co‐morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest. |
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