Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial The PROSIT-BIO Cohort: A Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Infliximab Biosimilar 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 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 Results from a safety cohort of patients with renal anemia receiving the biosimilar epoetinzeta: The PASCO I study. Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients. Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations. Post-marketing study of biosimilar infliximab (CT-P13) to evaluate its safety and efficacy in Korea 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
BACKGROUND TNF inhibitors have improved treatment of Crohn 's disease , ulcerative colitis , spondyloarthritis , rheumatoid arthritis , psoriatic arthritis , and chronic plaque psoriasis , but are expensive therapies . The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy , safety , and immunogenicity . METHODS The study is a r and omised , non-inferiority , double-blind , phase 4 trial with 52 weeks of follow-up . Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation . Patients with informed consent were r and omised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment , with unchanged dosing regimen . Data were collected at infusion visits in 40 Norwegian study centres . Patients , assessors , and patient care providers were masked to treatment allocation . The primary endpoint was disease worsening during 52-week follow-up .  394 patients in the primary per- protocol set were needed to show a non-inferiority margin of 15 % , assuming 30 % disease worsening in each group . This trial is registered with Clinical Trials.gov , number NCT02148640 . FINDINGS Between Oct 24 , 2014 , and July 8 , 2015 , 482 patients were enrolled and r and omised ( 241 to infliximab originator , 241 to CT-P13 group ; one patient was excluded from the full analysis and safety set for CT-P13 ) and 408 were included in the per- protocol set ( 202 in the infliximab originator group and 206 in the CT-P13 group ) . 155 ( 32 % ) patients in the full analysis set had Crohn 's disease , 93 ( 19 % ) had ulcerative colitis , 91 ( 19 % ) had spondyloarthritis , 77 ( 16 % ) had rheumatoid arthritis , 30 ( 6 % ) had psoriatic arthritis , and 35 ( 7 % ) had chronic plaque psoriasis . Disease worsening occurred in 53 ( 26 % ) patients in the infliximab originator group and 61 ( 30 % ) patients in the CT-P13 group ( per- protocol set ; adjusted treatment difference -4·4 % , 95 % CI -12·7 to 3·9 ) . The frequency of adverse events was similar between groups ( for serious adverse events , 24 [ 10 % ] for infliximab originator vs 21 [ 9 % ] for CT-P13 ; for overall adverse events , 168 [ 70 % ] vs 164 [ 68 % ] ; and for adverse events leading to discontinuation , nine [ 4 % ] vs eight [ 3 % ] , respectively ) . INTERPRETATION The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15 % . The study was not powered to show non-inferiority in individual diseases . FUNDING Norwegian Ministry of Health and Care Services Background : Few data are available on the safety and efficacy of infliximab biosimilar CT-P13 in patients with ulcerative colitis and Crohn 's disease . Methods : A prospect i ve , multicenter , cohort study using a structured data base . Results : Consecutive patients ( 313 Crohn 's disease and 234 ulcerative colitis ) were enrolled from 31 referral centers ; 311 patients were naive to anti – tumor necrosis factor alpha , 139 had a previous exposure to biologics , and the remaining 97 were switched to CT-P13 after a mean of 18 ± 14 infusions of infliximab .  The mean follow-up was 4.3 ± 2.8 months , and the total follow-up time was 195 patient-years . After 2061 infusions , 66 serious adverse events were reported ( 12.1 % ) , 38 ( 6.9 % ) of them were infusion-related reactions . The biosimilar had to be stopped in 29 ( 5.3 % ) cases for severe infusion reactions ( 8 naive , 19 previous exposed , and 2 switch ) , and in further 16 patients ( 2.9 % ) for other serious adverse events . Infusion reactions were significantly more frequent in patients pre-exposed to infliximab than to other anti – tumor necrosis factor alpha ( incidence rate ratio = 2.82 , 95 % CI : 1.05–7.9 ) . The efficacy of the biosimilar was evaluated in 434 patients who received treatment for at least 8 weeks , using time-to-event methods for censored observations : 35 patients were primary failures ( 8.1 % ) . After further 8 , 16 , and 24 weeks , the efficacy estimations were 95.7 % , 86.4 % , and 73.7 % for naive , 97.2 % , 85.2 % , and 62.2 % for pre-exposed , and 94.5 % , 90.8 % , and 78.9 % for switch , respectively ( log-rank P = 0.64 ) . Conclusions : Although no direct comparison was performed , preliminary data on efficacy and safety of CT-P13 were in line with those of infliximab 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 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 Epoetin-zeta ( epoetin-ζ ) ( sold as Retacrit ™ /Silapo ™ ) is a biologic product that was approved by the European Medicines Agency in 2007 after demonstrating biosimilarity to its reference product epoetin-α ( Eprex ™ ) , based on a comprehensive comparability exercise including extensive biophysical characterization and three double-blind r and omized controlled trials . Since 2008 , epoetin-ζ has been prescribed by physicians across Europe to treat anemia of renal disease in many thous and s of patients . METHODS Provided here are results of the PASCO I study ( post-authorization safety cohort observation of silapo/retacrit ( epoetin-ζ ) administered intravenously for the treatment of renal anemia ) . The primary study endpoint was the frequency of adverse events of special interest ( AESI ) occurring in patients receiving epoetin-ζ  over a 1-year study observation period . RESULTS The safety set included 1,634 patients who received at least 1 dose of epoetin-ζ during the study period . These patients experienced AESI at these frequencies : clotting of artificial kidney 9.8 % , lack of efficacy 2.3 % , cerebrovascular events ( including cerebrovascular accident , cerebral infa rct ion , cerebral hemorrhage , and transient ischemic attack ) 1.8 % , myocardial infa rct ion 1.7 % , acute myocardial infa rct ion 1.2 % , clinical ly relevant hyperkalemia 0.4 % , deep vein thrombosis 0.2 % , convulsion 0.2 % , hypertensive encephalopathy 0.1 % , and pulmonary embolism 0.1 % . No patients were reported as having anaphylactoid reactions , angioedema , erythropoietinneutralizing antibodies , or pure red cell aplasia . The median weekly follow-up dose of epoetin-ζ was 158.6 IU/kg . Mean hemoglobin concentration ranged between 11.3 and 11.7 g/dL. From the safety set , 228 patients died ( 14.0 % ) , while 1,135 patients ( 74.9 % ; excluding 119 with data missing ) continued treatment with epoetin-ζ following the 12-month observation . CONCLUSION The PASCO I study contributes significantly to current knowledge about the frequency of adverse events associated with the use of epoetin-ζ for the treatment of renal anemia and demonstrates a pattern of adverse events comparable with data for other existing epoetin products in Europe Anemia is a frequent complication in patients with chronic kidney disease . However , human recombinant erythropoietin ( rHu-EPO ) has revolutionized the management of anemia in chronically dialyzed patients .  Epomax ® is a new rHu-EPO alfa manufactured in Tunisia ( Medis Laboratories ) . The aim of this study was to evaluate the efficacy and tolerance of Epomax ® in chronic hemodialysis ( HD ) patients in a phase-III , multicenter , clinical trial . Fiftythree HD patients ( mean age 47.7 ± 13 years ) who received a stable dose of rHu-EPO ( Hemax ® , a rHu-EPO alfa manufactured by Biosidus Laboratories ) subcutaneously were switched to Epomax ®  via the same route of administration . At baseline , the mean systolic pressure was 132 ± 18 mm Hg and the mean diastolic pressure was 79 ± 8 mm Hg . The mean blood hemoglobin was 10.2 g/dL and the median ferritin level was 667 ng/mL. After a follow-up of 43 days , the mean blood hemoglobin was 10.5 g/dL under the effect of Epomax ® . There was no significant difference in the mean hemoglobin levels between the treatments with both drugs . Few adverse events were reported during the study . We conclude that Epomax ® was effective at maintaining the hemoglobin levels at target concentrations and was well tolerated in HD patients 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 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 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
INTRODUCTION While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice , switching clinical ly stable patients from an originator to a biosimilar is an issue for clinicians .
Well- design ed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited , especially for monoclonal antibodies .