Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial Infliximab in active early rheumatoid arthritis Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-contro Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial. A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis. Histological changes in bone marrow after treatment of infliximab for rheumatoid arthritis Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. Effectiveness, predictive response factors, and safety of anti-tumor necrosis factor (TNF) therapies in anti-TNF-naive rheumatoid arthritis.
BACKGROUND Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate , a st and ard treatment for this disease . There is evidence that antitumour necrosis factor alpha ( TNFalpha ) is efficacious in relief of signs and symptoms . We therefore investigated whether infliximab , a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate .  METHODS In an international double-blind placebo-controlled phase III clinical trial , 428 patients who had active rheumatoid arthritis , who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks , were r and omised to placebo ( n=88 ) or one of four regimens of  infliximab  at weeks 0 , 2 , and 6 . Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate ( median 15 mg/week for > or = 6 months , range 10 - 35 mg/wk ) . Patients were assessed every 4 weeks for 30 weeks . FINDINGS At 30 weeks , the American College of Rheumatology ( 20 ) response criteria , representing a 20 % improvement from baseline , were achieved in 53 , 50 , 58 , and 52 % of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks , respectively , compared with 20 % of patients receiving placebo plus methotrexate ( p<0.001 for each of the four infliximab regimens vs placebo ) . A 50 % improvement was achieved in 29 , 27 , 26 , and 31 % of infliximab plus methotrexate in the same treatment groups , compared with 5 % of patients on placebo plus methotrexate ( p<0.001 ) . Infliximab was well-tolerated ; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group . INTERPRETATION During 30 weeks , treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate Objective : To examine the impact of the combination of infliximab plus methotrexate ( MTX ) on the progression of structural damage in patients with early rheumatoid arthritis ( RA ) . Methods : Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy ( ATTRACT ) study , in which 428 patients with active RA despite MTX therapy received placebo with MTX ( MTX-only ) or infliximab 3 mg/kg or 10 mg/kg every ( q ) 4 or 8 weeks with MTX ( infliximab plus MTX ) for 102 weeks . Early RA was defined as disease duration of 3 years or less ; 82 of the 428 patients ( 19 % ) met this definition . Structural damage was assessed with the modified van der Heijde-Sharp score . The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group . Results : The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen . Consistent benefit was seen in the joints of both h and s and feet . Conclusions : Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment . Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity Objective : To evaluate the effect of infliximab dose escalation in incomplete responders in a r and omised controlled trial . Methods : 141 rheumatoid arthritis ( RA ) patients treated with infliximab for 12 months ( 3 mg/kg ; intervals 0 , 2 , 6 and then 8 weeks ) who responded to the drug ( disease activity score in 28 joints ( DAS28 ) decrease > 1.2 ) but who were not in remission ( DAS28 > 2.6 ) were enrolled into the study . Patients were r and omly assigned into arm A , 3 mg/kg , and arm B , 5 mg/kg infliximab every 8 weeks . Outcome measures included the DAS28 , its components and C-reactive protein ( CRP ) . Results : There were no significant differences in changes in the DAS28 , its components , or CRP in patients in arms A and B during the 12 months of treatment . All patients showed a DAS28 decrease greater than 0.6 after 28 weeks . Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2 % and 28.2 % of arm A patients and in 7.2 % and 47.8 % of arm B patients . The frequency of serious adverse events was comparable between arms A and B ( 16.9 % and 15.9 % , respectively ) , and the frequency of serious infections was not significantly greater in the higher dose group ( 5.8 % ) than in the lower dose group ( 5.6 % ) . Conclusions : In this setting , increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity . These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders Objectives : This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo . The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score ( based on erythrocyte sedimentation rates ; DAS28 ( ESR ) ) for the abatacept vs placebo groups at day 197 . Methods : Patients with rheumatoid arthritis ( RA ) and an inadequate response to methotrexate ( MTX )  were r and omised 3:3:2 to abatacept ( ∼10 mg/kg every 4 weeks , n = 156 ) , infliximab ( 3 mg/kg every 8 weeks , n = 165 ) , or placebo ( every 4 weeks , n = 110 ) and background MTX .  Safety and efficacy were assessed throughout the study . Results : Similar patient demographics and clinical characteristics were present at baseline between groups , with mean scores of ∼1.7 for HAQ-DI and 6.8 for DAS28 ( ESR ) . At 6 months , mean changes in DAS28 ( ESR ) were significantly greater for abatacept vs placebo ( –2.53 vs –1.48 , p<0.001 ) and infliximab vs placebo ( –2.25 vs –1.48 , p<0.001 ) . For abatacept vs infliximab treatment at day 365 , reductions in the DAS28 ( ESR ) were –2.88 vs –2.25 . At day 365 , the following response rates were observed for abatacept and infliximab , respectively : American College of Rheumatology ( ACR ) 20 , 72.4 and 55.8 % ; ACR 50 , 45.5 and 36.4 % ; ACR 70 , 26.3 and 20.6 % ; low disease activity score ( LDAS ) , 35.3 and 22.4 % ; DAS28-defined remission , 18.7 and 12.2 % ; good European League Against Rheumatism ( EULAR ) responses , 32.0 and 18.5 % ; and Health Assessment Question naire Disability Index ( HAQ-DI ) , 57.7 and 52.7 % . Mean changes in physical component summary ( PCS ) were 9.5 and 7.6 , and mental component summary ( MCS ) were 6.0 and 4.0 , for abatacept and infliximab , respectively . Over 1 year , adverse events ( AEs ) ( 89.1 vs 93.3 % ) , serious AEs ( SAEs ) ( 9.6 vs 18.2 % ) , serious infections ( 1.9 vs 8.5 % ) and discontinuations due to AEs ( 3.2 vs 7.3 % ) and SAEs ( 2.6 vs 3.6 % ) were lower with abatacept than infliximab . Conclusions : In this study , abatacept and infliximab ( 3 mg/kg every 8 weeks ) demonstrated similar efficacy . Overall , abatacept had a relatively more acceptable safety and tolerability profile , with fewer SAEs , serious infections , acute infusional events and discontinuations due to AEs than the infliximab group . Trial registration number : NCT00095147 OBJECTIVE Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis ( RA ) . However , their optimal use is yet to be determined . This 12-month double-blind study attempted remission induction using st and ard therapy with or without infliximab in patients with early , poor-prognosis RA . The primary end point was synovitis ( measured by magnetic resonance imaging [ MRI ] ) . Clinical observations continued to 24 months . METHODS All patients had fewer than 12 months of symptoms . Assessment s included full metrologic evaluation , laboratory tests , radiographs , functional evaluation using the Health Assessment Question naire ( HAQ ) , and quality of life measurement using the RA Quality of Life ( RAQoL ) question naire . MRI was performed at 0 , 4 , 14 , and 54 weeks ; MR images were scored blindly . Patients received methotrexate ( MTX ) and were r and omized to receive either infliximab or placebo for 12 months . RESULTS Twenty patients were recruited ( mean age 52 years , mean symptom duration 6 months , mean C-reactive protein level 42 mg/liter , and 65 % rheumatoid factor positive ) . At 1 year , all MRI scores were significantly better , with no new erosions in the infliximab plus MTX group ; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology ( ACR ) 50 % and 70 % improvement criteria ( 78 % versus 40 % in the placebo plus MTX group and 67 % versus 30 % , respectively ) and had a greater functional benefit ( P < 0.05 for all comparisons ) . Importantly , at 1 year after stopping induction therapy , response was sustained in 70 % of the patients in the infliximab plus MTX group , with a median Disease Activity Score in 28 joints ( DAS28 ) of 2.05 ( remission range ) . At 2 years , there were no significant between-group differences in the DAS28 , ACR response , or radiographic scores , but differences in the HAQ and RAQoL scores were maintained ( P < 0.05 ) . CONCLUSION Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year . At 2 years , functional and quality of life benefits were sustained , despite withdrawal of infliximab therapy . These data may have significant implication s for the optimal use of expensive biologic therapies OBJECTIVE To compare the benefits of initiating treatment with methotrexate ( MTX ) and infliximab ( anti-tumor necrosis factor alpha [ anti-TNFalpha ] monoclonal antibody ) with those of MTX treatment alone in patients with rheumatoid arthritis ( RA ) of < or =3 years ' duration . METHODS RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor . One thous and forty-nine patients were r and omly assigned in a 4:5:5 ratio to 3 treatment groups : MTX-placebo , MTX-3 mg/kg infliximab , and MTX-6 mg/kg infliximab . MTX dosages were rapidly escalated to 20 mg/week , and infliximab or placebo infusions were given at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 46 . RESULTS At week 54 , the median percentage of American College of Rheumatology improvement ( ACR-N ) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group ( 38.9 % and 46.7 % versus 26.4 % , respectively ; P < 0.001 for both comparisons ) . Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone ( mean + /- SD changes in van der Heijde modification of the total Sharp score at week 54 : 0.4 + /- 5.8 and 0.5 + /- 5.6 versus 3.7 + /- 9.6 , respectively ; P < 0.001 for each comparison ) . In addition , physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group . Infliximab therapy was associated with a significantly higher incidence of serious infections , especially pneumonia . CONCLUSION For patients with active RA in its early stages , combination therapy with MTX and infliximab provides greater clinical , radiographic , and functional benefits than treatment with MTX alone OBJECTIVE To assess the relationship between inflammation and joint destruction in rheumatoid arthritis ( RA ) patients who have not responded clinical ly to treatment . METHODS Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab ( 3 mg/kg or 10 mg/kg every 4 or 8 weeks ) plus methotrexate ( MTX ) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial . RESULTS At week 54 , patients who did not show 20 % improvement by American College of Rheumatology criteria ( ACR20 nonresponders ) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables , including the 28-joint Disease Activity Score ( DAS28 ) ( P < 0.001 ) , tender joint count ( P = 0.014 ) , swollen joint count ( P < 0.001 ) , and C-reactive protein ( CRP ) level ( P < 0.001 ) . Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment , radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited ( P < 0.001 ) compared with ACR20 nonresponders to MTX plus placebo .  Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX , irrespective of ACR response status ( mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group , versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group ) . Furthermore , among patients who were ACR20 nonresponders through week 54 , patients who were DAS nonresponders at weeks 30 and 54 , and patients without any improvement in individual clinical variables , those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo ( P < 0.05 to P < 0.001 ) . CONCLUSION Even in patients without clinical improvement , treatment with infliximab plus MTX provided significant benefit with regard to the destructive process , suggesting that in such patients these 2 measures of disease are dissociated BACKGROUND Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone . We aim ed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis . METHODS In a double-blind , r and omised , clinical efficacy , safety , and radiographic study , 686 patients with active rheumatoid arthritis were r and omly allocated to treatment with etanercept 25 mg ( subcutaneously twice a week ) , oral methotrexate ( up to 20 mg every week ) , or the combination . Clinical response was assessed by criteria of the American College of Rheumatology ( ACR ) . The primary efficacy endpoint was the numeric index of the ACR response ( ACR-N ) area under the curve ( AUC ) over the first 24 weeks . The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score . Analysis was by intention to treat . FINDINGS Four patients did not receive any drug ; thus 682 were studied .  ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone ( 18.3%-years [ 95 % CI 17.1 - 19.6 ] vs 14.7%-years [ 13.5 - 16.0 ] , p<0.0001 , and 12.2%-years [ 11.0 - 13.4 ] , p<0.0001 ; respectively ) . The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 ( 95 % CI 4.5 - 7.8 , p<0.0001 ) and between etanercept and methotrexate was 2.5 ( 0.8 - 4.2 , p=0.0034 ) . The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage ( mean total Sharp score -0.54 [ 95 % CI -1.00 to -0.07 ] vs 2.80 [ 1.08 to 4.51 ] , p<0.0001 , and 0.52 [ -0.10 to 1.15 ] , p=0.0006 ; respectively ) . The mean difference in total Sharp score between combination and methotrexate alone was -3.34 ( 95 % CI -4.86 to -1.81 , p<0.0001 ) and between etanercept and methotrexate was -27 ( -3.81 to -0.74 , p=0.0469 ) . The number of patients reporting infections or adverse events was similar in all groups . INTERPRETATION The combination of etanercept and methotrexate was significantly better in reduction of disease activity , improvement of functional disability , and retardation of radiographic progression compared with methotrexate or etanercept alone . These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis OBJECTIVE To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis ( RA ) treated with methotrexate ( MTX )  versus those treated with infliximab plus MTX . METHODS Patients who had not previously been treated with MTX with active RA were r and omly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 46 . Radiographic joint damage was assessed using the modified Sharp/van der Heijde score ( SHS ) . The relationship between disease activity measures at baseline and week 14 , as well as those averaged over time , were examined in relation to the change in SHS from baseline through week 54 . RESULTS C-reactive protein ( CRP ) levels , erythrocyte sedimentation rate ( ESR ) , and swollen joint count were associated with greater joint damage progression in the MTX-only group , while none of these parameters was associated with progression in the infliximab plus MTX group . Mean changes in SHS among patients in the highest CRP ( > or = 3 mg/dl ) and ESR ( > or = 52 mm/hour ) tertiles in the MTX-only group were 5.62 and 5.89 , respectively , compared with 0.73 and 1.12 in the infliximab plus MTX group ( P < 0.001 ) . Patients with greater joint damage at baseline ( SHS > or = 10.5 ) showed less progression with infliximab plus MTX compared with MTX alone ( -0.39 versus 4.11 ; P < 0.001 ) . Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab . CONCLUSION High CRP level , high ESR , or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone , while little radiographic progression was seen in patients receiving both MTX and infliximab , regardless of the abnormal levels of these traditional predictors OBJECTIVE To determine whether the rate of serious infection is higher in  anti-tumor necrosis factor (anti-TNF)-treated rheumatoid arthritis ( RA ) patients compared with RA patients treated with traditional disease-modifying antirheumatic drugs ( DMARDs ) .  METHODS This was a national prospect i ve observational study of 7,664 anti-TNF-treated and 1,354 DMARD-treated patients with severe RA from the British Society for Rheumatology Biologics Register . All serious infections , stratified by site and organism , were included in the analysis . RESULTS Between December 2001 and September 2005 , there were 525 serious infections  in the  anti-TNF-treated cohort and 56 in the comparison cohort ( 9,868 and 1,352 person-years of followup , respectively ) . The incidence rate ratio ( IRR ) , adjusted for baseline risk , for the anti-TNF-treated cohort compared with the comparison cohort was 1.03 ( 95 % confidence interval 0.68 - 1.57 ) . However , the frequency of serious skin and soft tissue infections was increased in  anti-TNF-treated patients , with an adjusted IRR of 4.28 ( 95 % confidence interval 1.06 - 17.17 ) . There was no difference in infection risk between the 3 main anti-TNF drugs . Nineteen serious bacterial intracellular infections occurred , exclusively in patients in the anti-TNF-treated cohort . CONCLUSION In patients with active RA , anti-TNF therapy was not associated with increased risk of overall serious infection compared with DMARD treatment , after adjustment for baseline risk . In contrast , the rate of serious skin and soft tissue infections was increased , suggesting an important physiologic role of TNF in host defense in the skin and soft tissues beyond that in other tissues OBJECTIVE To assess the risk of serious infections following 22 weeks of infliximab therapy , and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis ( RA ) with various comorbidities . METHODS Patients with active RA despite receiving methotrexate ( MTX )  were r and omly assigned to receive infusions of placebo ( group 1 , n=363 ) , 3 mg/kg infliximab ( group 2 , n=360 ) , or 10 mg/kg infliximab ( group 3 , n=361 ) at weeks 0 , 2 , 6 , and 14 . At week 22 , patients in placebo group 1 began receiving 3 mg/kg infliximab , and patients in group 3 continued to receive an infliximab dose of 10 mg/kg . Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg . RESULTS At week 22 , the relative risk of developing serious infections in groups 2 and 3 , compared with group 1 , was 1.0 ( 95 % confidence interval [ 95 % CI ] 0.3 - 3.1 , P=0.995 ) and 3.1 ( 95 % CI 1.2 - 7.9 , P=0.013 ) , respectively . The incidence of serious adverse events was 7.8 % in groups 2 and 3 compared with 7.5 % in group 1 . From week 22 to week 54 , 11.8 % , 9.9 % , and 10.3 % of patients in groups 1 , 2 , and 3 , respectively , reported occurrences of serious adverse events . Through week 54 , 1 patient in group 1 , 2 patients in group 2 , and 4 patients in group 3 developed active tuberculosis . CONCLUSION The risk of serious infections in patients receiving the approved infliximab  dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone . Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22 OBJECTIVE A placebo controlled , double-blind trial ( DBT ) was conducted for Japanese patients with active rheumatoid arthritis ( RA ) despite treatment with low dose methotrexate ( MTX ) to evaluate the efficacy and safety of infliximab . Extended treatment with infliximab was conducted in an open-label trial ( OLT ) . METHODS In the DBT , 147 patients were r and omly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0 , 2 and 6 , combined with MTX . In the OLT , 129 patients from the DBT received 3 mg/kg infliximab  every 8 weeks . RESULTS The mean dose of MTX was 7.2 + /- 2.0 mg/week . Significantly more patients receiving 3 mg/kg ( 61.2 % ) and 10 mg/kg (52.9%)infliximab achieved a 20 % improvement according to the American College of Rheumatology ( ACR ) criteria at Week 14 , compared to placebo ( 23.4 % ) ( p < 0.001 ) . There was no significant difference in incidence of adverse events among the treatment groups . In patients receiving infliximab in the DBT , 11.6 % of patients with serum infliximab just before the OLT developed antibodies to infliximab ( ATI ) in the OLT , whereas 62.2 % of patients without serum infliximab did . In patients receiving placebo in the DBT , 43.9 % developed ATI . CONCLUSION The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study . The data from the DBT and OLT also supported the importance of an induction treatment of infliximab , followed by a maintenance treatment without a long interval , giving stable serum concentrations in order to prevent formation of ATI To investigate histological evidence of bone remodeling in response to infliximab for rheumatoid arthritis ( RA ) , bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty after treatment of infliximab for an average of 16 months ( range , 8–24 months ) . The patients had a mean age of 65.3 years ( range , 57–76 years ) with 4.8 mg/week of methotrexate ( MTX ; 4–6 mg ) and 3.8 mg/day of prednisolone ( 2–5 mg ) . Control sample s were obtained from ten RA patients who did not undergo infliximab therapy . These patients had an average age of 67.6 years ( range , 59–78 years ) and received 5.2 mg/week  of MTX ( 4–6 mg ) and 4.0 mg/day of prednisolone ( 2–5 mg ) . Histological examination of structural differences between the infliximab and control groups in bone marrow was performed using hematoxylin and eosin ( H & E ) to evaluate differences . In immunohistochemical examination , the expressions of tumor necrosis factor-α ( TNF-α ) , interleukin-6 ( IL-6 ) , receptor activator of nuclear ( kappa ) B lig and ( RANKL ) , osteoprotegerin ( OPG ) , and osteopontin ( OPN ) were compared between both groups . H & E staining revealed that the bone marrow tissues of the RA patients who underwent infliximab therapy demonstrated newly formed thickness of interstitial septum among the trabeculae as compared with the control group . Moreover , immunohistochemical examinations revealed that TNF-α , IL-6 , RANKL , OPG , and OPN were expressed in this newly formed bone after infliximab therapy . Therefore , treatment with infliximab improved the histological changes with respect to bone metabolism in the newly formed bone marrow tissues OBJECTIVE To investigate sensitive ultrasonographic imaging methods for detection of synovial thickness and vascularity to discriminate between patients with early rheumatoid arthritis ( RA ) receiving infliximab + methotrexate ( MTX ) versus placebo + MTX over 18 weeks , and to compare the relationship between synovial thickening and vascularity at baseline and radiologic damage to joints of the h and s and feet at 54 weeks . METHODS Patients with early RA ( duration <3 years ) receiving stable dosages of MTX  were r and omly assigned to receive blinded infusions of 5 mg/kg infliximab ( n = 12 ) or placebo ( n = 12 ) at weeks 0 , 2 , 6 , and then every 8 weeks until week 46 . At baseline and week 18 , clinical assessment s were performed , and metacarpophalangeal joints were assessed by high-frequency ultrasonography and power Doppler ultrasonography measurements . Radiographs of the h and s and feet taken at baseline and at 54 weeks were evaluated using the van der Heijde modification of the Sharp method ( vdH-Sharp score ) . RESULTS Using changes in the total vdH-Sharp score over 54 weeks and changes in synovial thickening and joint vascularity at 18 weeks , we were able to distinguish those patients receiving infusions of infliximab + MTX from those receiving placebo + MTX . Sonographic measurements of synovial thickening and vascularity at baseline in the placebo + MTX group demonstrated clear relationships with the magnitude of radiologic joint damage at week 54 . Infliximab + MTX treatment abolished these relationships . CONCLUSION The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks BACKGROUND Neutralization of tumor necrosis factor a ( TNF-alpha ) for three to six months reduces the symptoms and signs of rheumatoid arthritis . However , the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known . METHODS We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab , a chimeric monoclonal antibody against TNF-alpha  , in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks . We assessed clinical responses with use of the criteria of the American College of Rheumatology , the quality of life with a health-status question naire , and the effect on joint damage radiographically . RESULTS The combination of infliximab and methotrexate was well tolerated and result ed in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone ( clinical response , 51.8 percent vs. 17.0 percent ; P<0.001 ) . The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone . Radiographic evidence of joint damage increased in the group given methotrexate , but not in the groups given infliximab and methotrexate ( mean change in radiographic score , 7.0 vs. 0.6 , P<0.001 ) . Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response . CONCLUSIONS In patients with persistently active rheumatoid arthritis despite methotrexate therapy , repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage OBJECTIVE To evaluate the effectiveness and safety of anti-tumor necrosis factor ( anti-TNF ) therapies in rheumatoid arthritis ( RA ) , and to identify the factors involved in this response . METHODS Dynamic prospect i ve cohort study of patients with RA treated with anti-TNF under clinical practice conditions .  Effectiveness was evaluated using Disease Activity Score ( DAS ) 28 , European League Against Rheumatism ( EULAR ) response , Health Assessment Question naire ( HAQ ) , and time to treatment failure . Prior adherence was evaluated retrospectively and safety was evaluated by adverse events ( AE ) . The analysis was restricted to anti-TNF-naive patients . RESULTS The study included 161 patients treated for RA during 6 years ( 60 infliximab , 79 etanercept , and 22 adalimumab ) . At 6 months , 15 % reached a good EULAR response and 38 % a moderate response . A mean decrease of -1.5 ( p < 0.0001 ) was observed in the DAS28 and of -0.34 in the HAQ ( p < 0.0001 ) ; however , women showed poorer progress in terms of DAS and HAQ . In the first year , 64.3 % did not experience treatment failure and this figure was 50.5 % after 2 years . In one-third , glucocorticoids were withdrawn and in the remainder the dose was reduced by 50 % . Adherence to treatment , selection of etanercept , and intensification of infliximab were associated with a lower probability of premature failure in the multivariate model . AE were similar to other those in studies and no outst and ing differences in safety were found between the 3 anti-TNF therapies . CONCLUSIONS Anti-TNF treatments are effective and safe , reducing the activity of the disease , disability , and the need for corticosteroids . Patients who displayed good adherence prior to the anti-TNF treatment and were treated with etanercept or with increasing doses of infliximab had the best chance of displaying a response
Infliximab is a chimeric monoclonal antibody .
Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits .
The aim of this study is to evaluate the efficacy and safety of using infliximab for the treatment of rheumatoid arthritis .