A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study Efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study. Clinical Experience of the Use of CT-P13, a Biosimilar to Infliximab in Patients with Inflammatory Bowel Disease: A Case Series Clinical Outcomes Following a Switch from Remicade® to the Biosimilar CT-P13 in Inflammatory Bowel Disease Patients: A Prospective Observational Cohort Study. Switching from Remicade® to Remsima® is well Tolerated and Feasible: A Prospective, Open-label Study Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn’s disease and ulcerative colitis Appraisal of the Pediatric Crohn's Disease Activity Index on Four Prospectively Collected Datasets: Recommended Cutoff Values and Clinimetric Properties Evaluation of the Pediatric Crohn Disease Activity Index: A Prospective Multicenter Experience Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort Efficacy of Infliximab Biosimilar CT-P13 Induction Therapy on Mucosal Healing in Ulcerative Colitis. Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. Infliximab maintenance therapy for fistulizing Crohn's disease. Post-marketing study of biosimilar infliximab (CT-P13) to evaluate its safety and efficacy in Korea Efficacy of the new infliximab biosimilar CT-P13 induction therapy in Crohn’s disease and ulcerative colitis – experiences from a single center Biosimilar infliximab (CT-P13) in the treatment of inflammatory bowel disease: A Norwegian observational study Appraisal of the pediatric ulcerative colitis activity index (PUCAI) Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study.
Objectives To compare the efficacy and safety of innovator infliximab ( INX ) and CT-P13 , an INX biosimilar , in active rheumatoid arthritis patients with inadequate response to methotrexate ( MTX ) treatment . Methods Phase III r and omised , double-blind , multicentre , multinational , parallel-group study . Patients with active disease despite MTX ( 12.5–25 mg/week ) were r and omised to receive 3 mg/kg of CT-P13 ( n=302 ) or INX ( n=304 ) with MTX and folic acid . The primary endpoint was the American College of Rheumatology 20 % ( ACR20 ) response at week 30 . Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95 % CI for the treatment difference was within ±15 % . Secondary endpoints included ACR response criteria , European League Against Rheumatism ( EULAR ) response criteria , change in Disease Activity Score 28 ( DAS28 ) , Medical Outcomes Study Short-Form Health Survey ( SF-36 ) , Simplified Disease Activity Index , Clinical Disease Activity Index , as well as pharmacokinetic ( PK ) and pharmacodynamic ( PD ) parameters , safety and immunogenicity . Results At week 30 , ACR20 responses were 60.9 % for CT-P13 and 58.6 % for INX ( 95 % CI −6 % to 10 % ) in the intention-to-treat population . The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses ( C reactive protein ( CRP ) ) at week 30 were 85.8 % and 87.1 % , respectively . Low disease activity or remission according to DAS28–CRP , ACR – EULAR remission rates , ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30 . Incidence of drug-related adverse events ( 35.2 % vs 35.9 % ) and detection of antidrug antibodies ( 48.4 % vs 48.2 % ) were highly similar for CT-P13 and INX , respectively . Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30 , with a comparable PK profile and immunogenicity . CT-P13 was well tolerated , with a safety profile comparable with that of INX . Clinical Trials.gov Identifier Objectives To compare the pharmacokinetics ( PK ) , safety and efficacy of innovator infliximab ( INX ) and CT-P13 , a biosimilar to INX , in patients with active ankylosing spondylitis ( AS ) . Methods Phase 1 r and omised , double-blind , multicentre , multinational , parallel-group study . Patients were r and omised to receive 5 mg/kg of CT-P13 ( n=125 ) or INX ( n=125 ) . Primary endpoints were area under the concentration-time curve ( AUC ) at steady state and observed maximum steady state serum concentration ( Cmax , ss ) between weeks 22 and 30 . Additional PK , efficacy endpoints , including 20 % and 40 % improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria ( ASAS20 and ASAS40 ) , and safety outcomes were also assessed . Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX . Geometric mean Cmax , ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX . The ratio of geometric means was 104.5 % ( 90 % CI 94 % to 116 % ) for AUC and 101.5 % ( 90 % CI 95 % to 109 % ) for Cmax , ss . ASAS20 and ASAS40 responses at week 30 were 70.5 % and 51.8 % for CT-P13 and 72.4 % and 47.4 % for INX , respectively . In the CT-P13 and INX groups more than one adverse event occurred in 64.8 % and 63.9 % of patients , infusion reactions occurred in 3.9 % and 4.9 % , active tuberculosis occurred in 1.6 % and 0.8 % , and 27.4 % and 22.5 % of patients tested positive for anti-drug antibodies , respectively . Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS . CT-P13 was well tolerated , with an efficacy and safety profile comparable to that of INX up to week 30 BACKGROUND AND AIM The biosimilar of infliximab , CT-P13 , has recently been shown to be equivalent to infliximab in both efficacy and safety in the treatment of rheumatologic diseases . However , no data are available with respect to the drug 's efficacy in patients with inflammatory bowel disease ( IBD ) . We aim ed to assess the efficacy and safety of CT-P13 in IBD patients METHODS This was a retrospective multicenter study including both anti-tumor necrosis factor ( TNF ) naïve patients and patients who switched from the biologic originator to CT-P13 .  RESULTS In anti-TNF naïve Crohn 's disease ( CD ) patients ( n = 32 ) , clinical response and remission rates were 90.6 % and 68.8 % at week 2 , 90.6 % and 84.4 % at week 8 , 95.5 % and 77.3 % at week 30 , and 87.5 % and 75.0 % at week 54 , respectively . In anti-TNF naïve ulcerative colitis ( UC ) patients ( n = 42 ) , clinical response and remission rates were 76.2 % and 19.0 % at week 2 , 81.0 % and 38.1 % at week 8 , 91.3 % and 47.8 % at week 30 , and 100 % and 50.0 % at week 54 , respectively , while mucosal healing rates were 58.3 % at week 8 , 66.7 % at week 30 , and 66.7 % at week 54 . The efficacy of CT-P13 was maintained in 92.6 % ( 25/27 ) of CD patients and in 66.7 % ( 6/9 ) of UC patients after switching from its originator . Adverse events related to CT-P13 occurred in 11.8 % of UC patients . CONCLUSIONS CT-P13 appears to have comparable efficacy , safety , and interchangeability with its originator in the treatment of IBD . Further prospect i ve studies with long-term follow-up periods will be needed to confirm the biosimilarity of CT-P13 Background CT-P13 is the first biosimilar monoclonal antibody to infliximab . However , the antibody was tested only in rheumatoid arthritis and ankylosing spondylitis , which demonstrated equivalence to the originator in efficacy , safety , and pharmacokinetic profile . Extrapolation of its efficacy and safety to other pathologies is tenuous . Interchangeability with its originator is another unclear area . Aim We aim ed to describe the experience of CT-P13 use in inflammatory bowel disease at a tertiary center . Methods Seventeen subjects diagnosed with Crohn ’s disease ( CD , n = 8) or ulcerative colitis ( UC , n = 9 ) who were administered CT-P13 from November 2012 to October 2013 at Dongguk University Ilsan Hospital were retrospectively enrolled . Medical records analyzed included patients ’ characteristics , previous history of anti-tumor necrosis factor administration , response and remission to this biosimilar antibody , disease flare-up , and adverse drug reaction . Results Male – female ratio was 1.8 . Mean age was 35.4 years ( range 15–57 ) . Mean number of CT-P13 administrations was 4.2 ± 1.9 . Induction treatments were done in five UC and three CD patients . Clinical response and remission at 8 weeks were achieved in seven patients ( five UC and two CD ) . One CD patient did not respond to CT-P13 . Nine patients in maintenance with the originator were interchanged with CT-P13 ( four UC and five CD patients ) . One UC patient experienced arthralgia  and CT-P13 was discontinued . One patient experienced loss of response during the study period . Conclusions CT-P13 may have biosimilarity and interchangeability with its originator in inflammatory bowel disease . A large , r and omized , double-blind , prospect i ve study is needed BACKGROUND AND AIMS The biosimilar of Remicade ® , CT-P13 , recently entered the European market . Clinical data on switching from Remicade ® to CT-P13 in inflammatory bowel disease [ IBD ] are scarce . We aim ed to prospect ively investigate efficacy , safety , pharmacokinetic profile , and immunogenicity following a switch from Remicade ® to CT-P13 in IBD patients . METHODS  Remicade ® -treated IBD patients at the Radboud university medical centre who switched to CT-P13 were included in this prospect i ve observational cohort study . Primary endpoint was change in Harvey-Bradshaw Index for Crohn 's disease [ CD ] and Simple Clinical Colitis Activity Index for ulcerative colitis [ UC ] at week 16 . We measured C-reactive protein [ CRP ] , faecal calprotectin [ FCP ] , infliximab trough level [ TL ] and anti-drug antibodies [ ADAs ] and documented adverse events . RESULTS Our cohort consisted of 83 patients ( 28 males , 57 CD , 24 UC , 2 IBD-unclassified [ IBD-U ] ) . The median age was 36 years , range 18 - 79 . Median change in disease activity was 0 [ range -23 to + 7 ] for CD and 0 [ range -3 to + 6 ] for UC/IBD-U. Median CRP and FCP levels did not change significantly during follow-up . Median TL increased from 3.5 µg/ml [ range 0 - 18 ] to 4.2 µg/ml [ range 0 - 21 ] at week 16 [ p = 0.010 ] . Two patients developed a new detectable ADA response during follow-up and five patients discontinued CT-P13 . No serious adverse events occurred . CONCLUSIONS We demonstrated that switching from Remicade ® to CT-P13 in a real-life cohort of IBD patients did not have a significant impact on short-term clinical outcomes . These results suggest that switching from Remicade ® to CT-P13 for the treatment of IBD is feasible Background and Aims A biosimilar version of infliximab [ CT-P13/Remsima ® ] recently entered the European market . The clinical data on its use in inflammatory bowel disease [ IBD ] are sparse , especially on switching from the originator Remicade ® . In this study , we aim ed to prospect ively investigate the feasibility , safety and immunogenicity of switching from Remicade to Remsima in a real-life IBD population . Methods All adult patients who were treated with Remicade in the Department of Gastroenterology at Oslo University Hospital were switched to Remsima . The follow-up lasted for 6 months . In addition , a retrospective registration was performed with a start time of 6 months before switching drugs . The primary endpoints were [ i ] the proportion of patients remaining on medication 6 months after switching and [ ii ] adverse events during the 6 months after switching . The secondary endpoints included [ i ] disease activity scores [ Harvey-Bradshaw Index and Partial Mayo Score ] , C-reactive protein , haemoglobin , faecal calprotectin , infliximab dose and interval , and p-infliximab and [ ii ] the development of antidrug antibodies . Results In total , 143 IBD patients were switched , 99 with Crohn 's disease and 44 with ulcerative colitis . The large majority [ 97 % ] remained on the medication throughout follow-up . A low number of adverse events were observed . No change in disease activity , C-reactive protein , haemoglobin , faecal calprotectin , infliximab dose and interval or p-infliximab was detected . Three patients developed new detectable antidrug antibodies . Conclusions Switching from Remicade to Remsima was feasible and with few adverse events , including very limited antidrug antibody formation and loss of response Abstract Objective : The infliximab biosimilar CT-P13 ( Remsima ® , Inflectra ® ) was approved in Europe for the treatment of inflammatory bowel disease ( IBD ) based on extrapolation of data from patients with rheumatic disease . Because there are limited published reports on clinical outcomes for IBD patients treated with CT-P13  , we monitored responses to induction treatment with this biosimilar in patients with Crohn ’s disease ( CD ) or ulcerative colitis ( UC ) in centres across the Czech Republic . Material and methods : Fifty-two patients with CD ( n = 30 ) or UC ( n = 22 ) were treated with 5 mg/kg CT-P13 for up to 14 weeks . Effectiveness of therapy was evaluated with the Crohn ’s Disease Activity Index ( CDAI ) or the Mayo Scoring System ( MSS ) in patients with CD or UC , respectively , before and after 14 weeks . Additional goals were to evaluate weight changes , serum C-reactive protein ( CRP ) levels , and complications/adverse events . Results : In patients with CD , remission ( CDAI < 150 ) was achieved in 50.0 % of cases , and partial response ( ≥70-point decrease in CDAI score from baseline ) in the remaining 50.0 % . In patients with UC , remission ( total score on partial Mayo index ≤2 points ) was achieved in 40.9 % of cases , partial response ( ≥2-point decrease in partial Mayo score from baseline ) in 54.5 % , and no response in 4.5 % . There were statistically significant improvements in CDAI , MSS and CRP serum levels after 14 weeks of therapy , and body weight increased . Four adverse events were identified ( n = 1 each ) : lower-extremity phlebothrombosis , herpes labialis , pneumonia and allergic reaction . Conclusions : This prospect i ve observational study provides evidence of the effectiveness of CT-P13 in IBD OBJECTIVES : The Pediatric Crohn 's Disease Activity Index ( PCDAI ) is the outcome measure of choice in clinical trials of pediatric Crohn 's disease . The aim of this study was to provide knowledge on its performance and accuracy of different cutoff scores . METHODS : Longitudinal data prospect ively generated from four sources were used , including the REACH and budesonide trials , a North-American inflammatory bowel diseases ( IBD ) registry , and a cohort aim ed at evaluating growth . Cutoff values of disease activity were determined by physician global assessment from the pooled cohort using serial receiver operator characteristic curves and area under the curve ( AUC ) as well as comparing the overall accuracy . Test – retest reliability and responsiveness were ascertained by comparing the baseline and follow-up scores , using an external anchor . RESULTS : A total of 437 children were included ( 268 ( 61 % ) males , mean age 12.9±2.6 years ) . To define remission , a composite definition of < 10 points or < 7.5 points without the height item had the highest accuracy ; this addressed the limitation that height is not a responsive item . The best cutoff of 10–27.5 was determined for mild disease , 30–37.5 for moderate disease , 40–100 for severe disease , and a change of > 12.5 points for response ( AUC 0.8–0.9 ; P<0.001 ) . Ninety children whose disease remained unchanged showed fair test – retest reliability ( intraclass correlation coefficient=0.74–0.8 ; P<0.001 ) . The PCDAI showed good responsiveness , as reflected from the correlational ( r=0.7 ; P<0.001 ) , distributional ( Guyatt 's responsiveness statistics=0.9 ) , and diagnostic utility analysis ( AUC 0.85 ( 95 % confidence interval 0.81–0.88 ) . CONCLUSIONS : The clinimetric properties of the PCDAI are sufficient to support its use in clinical research . Cutoff values suggested by this study differ slightly from those previously published on much smaller cohorts Background and Objectives : Longitudinal assessment of disease activity is necessary for studies of therapeutic intervention in children with Crohn disease . The Pediatric Crohn Disease Activity Index ( PCDAI ) was developed a decade ago for such a purpose , but it function has only been examined in a small number of studies with a limited number of patients . The primary objectives of the present study were to develop cut scores reflecting disease activity as determined by physician global assessment ( PGA ) and to evaluate the responsiveness of the PCDAI to changes in patient condition after therapeutic interventions . Methods : Data were derived from a prospect i ve data base of newly diagnosed children with inflammatory bowel disease established in 2002 at 18 pediatric gastroenterology centers in the United States and Canada . At diagnosis , at 30 days and 3 months after diagnosis , and quarterly thereafter , children ( < 16 years of age ) with Crohn disease had disease assessment performed by PGA and PCDAI . Disease management was provided according to the dictates of the attending gastroenterologist and not by predetermined protocol . Results : 181 patients had concomitant PGA and PCDAI performed at diagnosis , and 95 of these had similar assessment at short-term follow up . Mean ± SD PCDAI scores for mild , moderate , and severe disease by PGA at diagnosis were 19.5 ± 10.4 , 32.2 ± 12.7 , and 47.8 ± 14.9 , respectively ( P < 0.001 for all comparisons ) . Mean ± SD PCDAI for inactive disease after treatment was 5.2 ± 5.4 . Receiver operating characteristic ( ROC ) curve analysis suggested that : 1 ) activity of moderate/severe disease was best reflected by a PCDAI of ≥30 points , 2 ) clinical response ( moderate/severe disease improving to mild/inactive ) was best reflected by a decrease in PCDAI of ≥12.5 points , and 3 ) a PCDAI < 10 best reflected inactive disease . Conclusions : PCDAI scores accurately reflect disease activity as assessed by physician global assessment . A PCDAI score of ≥30 has acceptable sensitivity and specificity to indicate disease of moderate/severe activity . A PCDAI decrease of 12.5 points or greater following therapeutic intervention accurately reflects a clinical ly significant response . The PCDAI is an appropriate tool for intervention trials in Crohn disease in children Background and aims : This observational study assessed the long-term clinical benefit of infliximab ( IFX ) in 614 consecutive patients with Crohn ’s disease ( CD ) from a single centre during a median follow-up of 55 months ( interquartile range ( IQR ) 27–83 ) . Methods : The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up . The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed . Results : 10.9 % of patients were primary non-responders to IFX .  Sustained benefit was observed in 347 of the 547 patients ( 63.4 % ) receiving long-term treatment . In 68.3 % of these , treatment with IFX was ongoing and in 31.7 % IFX was stopped , with the patient being in remission . Seventy patients ( 12.8 % ) had to stop IFX due to side effects and 118 ( 21.6 % ) due to loss of response . Although the yearly drop-out rates of IFX  in patients with episodic ( 10.7 % ) and scheduled treatment ( 7.1 % ) were similar , the need for hospitalisations and surgery decreased less in the episodic than in the scheduled group . Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group . Conclusions : In this large real-life cohort of patients with CD , long-term treatment with IFX was very efficacious to maintain improvement during a median follow-up of almost 5 years and changed disease outcome by decreasing the rate of hospitalisations and surgery INTRODUCTION CT-P13 is the first biosimilar to infliximab that has been approved for the same indications as its originator infliximab . No data are available on the effect of infliximab biosimilar on mucosal healing . The aim of this study was to evaluate the efficacy of CT-P13 induction therapy on mucosal healing in patients with ulcerative colitis [ UC ] . PATIENTS AND METHODS UC patients , who received CT-P13 therapy from its local introduction at three Hungarian and one Czech inflammatory bowel disease centres , were prospect ively enrolled .  Sigmoidoscopy was performed after the end of the induction therapy at week 14 . Mucosal healing was defined as Mayo endoscopic subscore 0 or 1 . Complete mucosal healing was defined as Mayo endoscopic subscore 0 . Trough level of CT-P13  was measured at week 14 . RESULTS Sixty-three UC patients who underwent CT-P13 induction therapy were enrolled in the study . Indication for the therapy was acute , severe flare up and chronic , refractory activity in 24 and 39 patients , respectively .  Cumulative clinical response and steroid-free remission at week 14 were achieved in 82.5 % and 47.6 % of the patients , respectively . Sigmoidoscopy revealed steroid-free mucosal healing in 47.6 % of the patients , and complete mucosal healing was present in 27 % . Mayo endoscopic subscore decreased significantly at week 14 compared to baseline . Trough levels of infliximab correlated with mucosal healing . CONCLUSION This is , to our knowledge , the first study examining the efficacy of CT-P13 induction therapy on mucosal healing in UC . The results indicate that mucosal healing is achieved in two-thirds of UC patients by the end of the induction treatment with CT-P13 Background : Several placebo controlled studies have demonstrated the efficacy of infliximab in inflammatory bowel disease ( IBD ) but the potential toxicity of this new biological compound has been less studied . Aim : To assess the use of infliximab in IBD in a population based cohort , with special emphasis on the occurrence of severe adverse events and mortality . Patients : All patients with IBD treated with infliximab between 1999 and 2001 in Stockholm County were evaluated . Methods : Prospect i ve registration of clinical data was carried out . Retrospective analyses were made of possible adverse events occurring in relation to infliximab treatment . Adverse events requiring pharmacological treatment or hospitalisation were defined as severe . Clinical response was assessed as remission , response , or failure . Results : A cohort comprising 217 patients was assembled : 191 patients had Crohn ’s disease ( CD ) , and infliximab was used off label for ulcerative colitis ( UC ) in 22 patients . Four patients were treated for indeterminate colitis ( IC ) . Mean age was 37.6 ( 0.9 ) years ( range 8–79 ) . The mean number of  infliximab infusions was 2.6 ( 0.1 ) ( range 1–11 ) . Forty two severe adverse events were registered in 41 patients ( CD , n = 35 ) . Eleven of the severe adverse events occurred postoperatively ( CD , n = 6 ) . Three patients with CD developed lymphoma ( of which two were fatal ) , opportunistic infections occurred in two patients ( one with UC , fatal ) , and two patients with severe attacks of IBD died due to sepsis ( one with CD , one postoperatively with UC ) . One additional patient with UC died from pulmonary embolism after colectomy . Mean age in the group with fatal outcome was 62.7 years ( range 25–79 ) . The overall response rate was 75 % and did not differ between the patient groups . Conclusions : Infliximab was efficacious as an anti-inflammatory treatment when assessed in a population based cohort of patients with IBD . However , there appear to be a significant risk of deleterious and fatal adverse events , particularly in elderly patients with severe attacks of IBD . Off label use of infliximab in UC and IC should be avoided until efficacy is proven in r and omised controlled trials . The underlying risk of developing malignancies among patients with severe or chronically active CD in need of infliximab treatment is not known but the finding of a 1.5 % annual incidence of lymphoma emphasises the need for vigilant surveillance with respect to this malignant complication Objectives To investigate the efficacy and safety of switching from infliximab reference product ( RP ) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis ( AS ) . Methods This open-label extension study recruited patients with AS who completed a 54-week , r and omised controlled study comparing CT-P13 with RP ( PLANETAS ) .  CT-P13 ( 5 mg/kg ) was administered intravenously every 8 weeks from week 62 to week 102 . Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20 . Antidrug antibodies ( ADAs ) were measured using an electrochemiluminescent method . Data were analysed for patients treated with CT-P13  in the main PLANETAS study and the extension ( maintenance group ) and those who were switched to CT-P13 during the extension study ( switch group ) . Results Overall , 174 ( 82.9 % ) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled . Among these , 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP . In these maintenance and switch groups , respectively , ASAS20 response rates at week 102 were 80.7 % and 76.9 % . ASAS40 and ASAS partial remission were also similar between groups . ADA positivity rates were comparable ( week 102 : 23.3 % vs 27.4 % ) . Adverse events led to treatment discontinuation during the extension study in 3 ( 3.3 % ) and 4 ( 4.8 % ) patients , respectively . Conclusions This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS . In the maintenance group , CT-P13 was effective and well tolerated over 2 years of treatment . Trial registration number NCT01571206 ; Results BACKGROUND AND AIMS The growing incidence of inflammatory bowel disease ( IBD ) in children necessitates the use of biological treatments . Recently , an infliximab biosimilar was authorized in the European Union , which may result in switching patients . We present our preliminary experiences with such switches . METHODS The prospect i ve study included 32 paediatric patients diagnosed with Crohn 's disease ( CD ) and 7 children with ulcerative colitis ( UC ) at 3 academic hospitals , who were switched from infliximab originator to its biosimilar ( Remsima ) .  Patient characteristics , disease severity , laboratory parameters and adverse events were recorded . Means , medians and ranges were calculated . RESULTS Mean age at diagnosis of CD and UC was 11.1 ( 2.7 - 15.3 ) and 12.3 years ( 8.5 - 14.8 ) , respectively .  Mean number of infliximab originator infusions before switching to the biosimilar was 9.9 ( median 8 , range 4 - 29 ) and 5.1 ( 5 , 1 - 12 ) for the CD and UC group , respectively . Evaluation efficacy of last biosimilar doses of all patients revealed rates of clinical remission of 88 and 57 % for CD and UC patients , respectively . Last follow-up assessment of patients who continued with biosimilar therapy showed that 16/20 ( 80 % ) CD patients and all 4 UC individuals were in remission . One infusion reaction to infliximab biosimilar was observed in a CD patient , which led to treatment discontinuation . The incidence of sporadic mild adverse events prior to and after switching did not differ significantly and was consistent with the safety profile of the infliximab molecule . CONCLUSION Switching from infliximab originator to its biosimilar seems to be a safe option in children with CD . After the switch the biosimilar was just as effective as the originator BACKGROUND Treatment with infliximab , a chimeric monoclonal IgG1 antibody against tumor necrosis factor , can result in the formation of antibodies against infliximab . We evaluated the clinical significance of these antibodies in patients with Crohn 's disease . METHODS In a cohort of 125 consecutive patients with Crohn 's disease who were treated with infliximab infusions  , we evaluated the concentrations of infliximab and of antibodies against infliximab  , clinical data , side effects ( including infusion reactions ) , and the use of concomitant medications before and 4 , 8 , and 12 weeks after each infusion . RESULTS A mean of 3.9 infusions ( range , 1 to 17 ) per patient were administered over a mean period of 10 months . Antibodies against infliximab  were detected in 61 percent of patients . The presence of concentrations of 8.0 microg per milliliter or greater before an infusion predicted a shorter duration of response ( 35 days , as compared with 71 days among patients with concentrations of less than 8.0 microg per milliliter ; P<0.001 ) and a higher risk of infusion reactions ( relative risk , 2.40 ; 95 percent confidence interval , 1.65 to 3.66 ; P<0.001 ) .  Infliximab concentrations were significantly lower at four weeks among patients who had had an infusion reaction than among patients who had never had an infusion reaction ( median , 1.2 vs. 14.1 microg per milliliter ; P<0.001 ) . Patients who had infusion reactions had a median duration of clinical response of 38.5 days , as compared with 65 days among patients who did not have an infusion reaction ( P<0.001 ) . Concomitant immunosuppressive therapy was predictive of low titers of antibodies against infliximab  ( P<0.001 ) and high concentrations of  infliximab  four weeks after an infusion ( P<0.001 ) . CONCLUSIONS The development of antibodies against infliximab is associated with an increased risk of infusion reactions and a reduced duration of response to treatment . Concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response BACKGROUND Infliximab , a monoclonal antibody against tumor necrosis factor , is an effective maintenance therapy for patients with Crohn 's disease without fistulas . It is not known whether infliximab is an effective maintenance therapy for patients with fistulas . METHODS We performed a multicenter , double-blind , r and omized , placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn 's disease and one or more draining abdominal or perianal fistulas of at least three months ' duration . Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0 , 2 , and 6 . A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then r and omly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54 . The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent r and omization . RESULTS The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance ( more than 40 weeks vs. 14 weeks , P<0.001 ) . At week 54 , 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas , as compared with 36 percent of patients in the infliximab maintenance group ( P=0.009 ) . CONCLUSIONS Patients with fistulizing Crohn 's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks Objective : To evaluate the safety and efficacy of CT-P13 ( Remsima ® ) in patients with inflammatory bowel disease ( IBD ) in South Korea . Methods : This post-marketing study included patients with active moderate-to-severe Crohn ’s disease ( CD ) , fistulizing CD ( FCD ) , or moderate-to-severe ulcerative colitis ( UC ) treated with CT-P13 and followed for 30 weeks . Assessment s included treatment-emergent adverse events ( TEAEs ) and disease-specific clinical response and remission . Results : No unexpected TEAEs were observed in the 173 patients recruited to date . TEAEs occurred in 18.1 , 16.7 , and 26.9 % of CD , FCD , and UC patients , respectively . Treatment-related TEAEs occurred in 10 % of patients and were mostly mild-moderate in severity . There were five serious TEAEs ( two infusion-related reactions , two infections , one abdominal pain ) and no cases of malignancy , pneumonia , or death . Positive outcomes for response/remission were reported regardless of whether patients had received prior infliximab or not . Conclusion : CT-P13 was well tolerated and efficacious in patients with IBD Background : CT-P13 is the first biosimilar monoclonal antibody to infliximab ( IFX ) ; it has been approved for the same indications as its IFX counterpart in Hungary . The aim of this study was to assess the efficacy of CT-P13 induction therapy in patients with Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) . Methods : Patients diagnosed with CD and UC , who were administered CT-P13 , were prospect ively enrolled . Disease activity was estimated at the start and after the induction therapy . In patients with UC , sigmoideoscopy was also performed at the end of the induction therapy . Results : Eighteen CD and 21 UC patients were enrolled . Induction treatment was completed in 16 of the CD and 15 of the UC patients . In those with luminal CD , clinical response and remission was achieved in 6 ( 37.5 % ) and 8 ( 50 % ) of the patients at Week 8 . In UC , clinical response and remission was achieved in 3 ( 20 % ) and 10 ( 66.7 % ) patients at Week 8 . Mucosal healing was shown in 11 patients . Conclusions : This was the first study to prospect ively evaluate the outcome of  CT-P13 induction therapy in CD and UC . Our results confirm that induction with CT-P13 is safe and effective Objective : To assess the efficacy , tolerability , and safety of CT-P13 ( Remsima ® ) in patients with Crohn ’s disease ( CD ) or ulcerative colitis ( UC ) . Methods : This was a prospect i ve observational study performed in a single center in Norway . Patients with CD ( n = 46 ) or UC ( n = 32 )  received CT-P13 ( 5 mg/kg ) by intravenous infusion at weeks 0 , 2 , and 6 . Efficacy end points included remission at week 14 , measured by a Harvey-Bradshaw Index score of ≤4 or partial Mayo score of ≤2 . Levels of the inflammatory markers C-reactive protein and calprotectin were measured . Adverse events up to week 14 were also recorded . Results : Seventy-nine percent of CD and 56 % of UC patients achieved remission at week 14 . Significant reductions in C-reactive protein and calprotectin occurred between baseline and week 14 . There were no unexpected adverse events reported during the study . Conclusion : CT-P13  is efficacious and well tolerated in patients with CD or UC Background : We evaluated the psychometric performance of the Pediatric Ulcerative Colitis Activity Index ( PUCAI ) in a real‐life cohort from the Pediatric IBD Collaborative Research Group . Methods : Two consecutive visits of 215 children with ulcerative colitis ( UC ) were included ( mean age 11.2 ± 3.6 years ; 112 ( 52 % ) males ; 63 ( 29 % ) newly diagnosed and the others after disease duration of 24 ± 15.6 months ) . Validity was assessed using several constructs of disease activity . Distributional and anchor‐based strategies were used to assess the responsiveness of the PUCAI to change over time following treatment . Results : Reflecting feasibility , 97.6 % of 770 eligible registry visits had a completed PUCAI score versus only 47.6 % for a contemporaneously collected Pediatric Crohn 's Disease Activity Index ( odds ratio = 45.8 , 95 % confidence interval [ CI ] 28.6–73.5 ) obtained for children with Crohn 's disease accessioned into the same data base . The PUCAI score was significantly higher in patients requiring escalation of medical therapy ( 45 points [ interquartile range , IQR , 30–60 ] ) versus those who did not , ( 0 points [ IQR 0–10 ] ; P < 0.001 ) , and was highly correlated with physician 's global assessment of disease activity ( r = 0.9 , P < 0.001 ) . The best cutoff to differentiate remission from active disease was 10 points ( area under receiver operating characteristic curve [ AUC ] 0.94 ; 95 % CI 0.90–0.97 ) . Test – retest reliability was excellent ( intraclass correlation coefficient = 0.89 ; 95 % CI 0.84–0.92 , P < 0.001 ) as well as responsiveness to change ( AUC 0.96 [ 0.92–0.99 ] ; st and ardized response mean 2.66 ) . Conclusion : This study on real‐life , prospect ively obtained data confirms that the PUCAI is highly feasible by virtue of the noninvasiveness , valid , and responsive index . The PUCAI can be used as a primary outcome measure to reflect disease activity in pediatric UC . ( Inflamm Bowel Dis 2009 Objectives To assess the efficacy and safety of switching from the infliximab reference product ( RP ; Remicade ) to its biosimilar CT-P13 ( Remsima , Inflectra ) or continuing CT-P13 in patients with rheumatoid arthritis ( RA ) for an additional six infusions . Methods This open-label extension study recruited patients with RA who had completed the 54-week , r and omised , parallel-group study comparing CT-P13 with RP ( PLANETRA ; NCT01217086 ) .  CT-P13 ( 3 mg/kg ) was administered intravenously every 8 weeks from weeks 62 to 102 . All patients received concomitant methotrexate . Endpoints included American College of Rheumatology 20 % ( ACR20 ) response , ACR50 , ACR70 , immunogenicity and safety . Data were analysed for patients who received CT-P13 for 102 weeks ( maintenance group ) and for those who received RP for 54 weeks and then switched to CT-P13 ( switch group ) . Results Overall , 302 of 455 patients who completed the PLANETRA study enrolled into the extension . Of these , 158 had received CT-P13 ( maintenance group ) and 144 RP ( switch group ) .  Response rates at week 102 for maintenance versus switch groups , respectively , were 71.7 % vs 71.8 % for ACR20 , 48.0 % vs 51.4 % for ACR50 and 24.3 % vs 26.1 % for ACR70 . The proportion of patients with antidrug antibodies was comparable between groups ( week 102 : 40.3 % vs 44.8 % , respectively ) . Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study ( 53.5 % and 53.8 % , respectively ) . Conclusions Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years . Trial registration number NCT01571219 ; Results BACKGROUND AND AIMS Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe . Prospect i ve data on its efficacy , safety , and immunogenicity in inflammatory bowel diseases are lacking . METHODS A prospect i ve , nationwide , multicentre , observational cohort was design ed to examine the efficacy , safety , and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn 's disease [ CD ] and ulcerative colitis [ UC ] . Demographic data were collected and a harmonised monitoring strategy was applied . Early clinical remission , response , and early biochemical response were evaluated at Week 14 , steroid-free clinical remission was evaluated at Week 30 . Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay . RESULTS In all , 210 consecutive inflammatory bowel disease [ 126 CD and 84 UC ] patients were included in the present cohort . At Week 14 , 81.4 % of CD and 77.6 % of UC patients showed clinical response and 53.6 % of CD and 58.6 % of UC patients were in clinical remission . Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve , compared with those with previous exposure to the originator compound [ p < 0.05 ] . Until Week 30 , adverse events were experienced in 17.1 % of all patients . Infusion reactions and infectious adverse events occurred in 6.6 % and 5.7 % of all patients , respectively . CONCLUSIONS This prospect i ve multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC . Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions BACKGROUND Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha , specifically chimeric monoclonal antibody cA2 , in the treatment of Crohn 's disease . METHODS We conducted a 12-week multicenter , double-blind , placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn 's disease that was resistant to treatment . All had scores on the Crohn 's Disease Activity Index between 220 and 400 ( scores can range from 0 to about 600 , with higher scores indicating more severe illness ) . Patients were r and omly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight , 10 mg per kilogram , or 20 mg per kilogram . Clinical response , the primary end point , was defined as a reduction of 70 or more points in the score on the Crohn 's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications . RESULTS At four weeks , 81 percent of the patients given 5 mg of cA2 per kilogram ( 22 of 27 patients ) , 50 percent of those given 10 mg of cA2 per kilogram ( 14 of 28 ) , and 64 percent of those given 20 mg of cA2 per kilogram ( 18 of 28 ) had had a clinical response , as compared with 17 percent of patients in the placebo group ( 4 of 24 ) ( p<0.001 for the comparison of the cA2 group as a whole with placebo ) . Thirty-three percent of the patients given cA2 went into remission ( defined as a score below 150 on the Crohn 's Disease Activity Index ) , as compared with 4 percent of the patients given placebo ( P=0.005 ) . At 12 weeks , 41 percent of the cA2-treated patients ( 34 of 83 ) had had a clinical response , as compared with 12 percent of the patients in the placebo group ( 3 of 25 ) ( P=0.008 ) . The rates of adverse effects were similar in the groups . CONCLUSIONS A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe , treatment-resistant Crohn 's disease Needing a single index of degree of illness in Crohn 's disease , the National Cooperative Crohn 's Disease Study group collected data prospect ively from 187 visits of 112 patients with Crohn 's disease of the small bowel , colon , or both . Information on 18 predictor variables was gathered at each visit . In addition , the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient 's status with that at the previous visit . A multiple regression computer program was utilized to derive an equation for prediction of the physician 's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints . This equation , numerically simplified and utilizing eight selected variables , is the Crohn 's Disease Activity Index . Index values of 150 and below are associated with quiescent disease ; values above that indicate active disease , and values above 450 are seen with extremely severe disease
Background Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases ( IBD ) .
However , many biological originators have reached , or are about to reach , patent expiry and long-term therapy costs have become progressively unsustainable .
CT-P13 , a biosimilar of the anti-tumor necrosis factor ( anti-TNF ) monoclonal antibody infliximab , might represent a significant alternative to its originator , with the potential to decrease medical care costs and , therefore , become available to a large number of patients .
Objectives In this systematic review , we analyzed the data from available clinical trials that recently investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in naïve patients and in patients who switched from its originator infliximab , focusing on clinical efficacy , safety and immunogenicity .