Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study

Summary Background The infliximab biosimilarCT-P13 was approved for use in Crohn's diseaseafter clinical comparison with originator infliximabin ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximabin patients with Crohn's diseasewho were naive to biological therapy. Methods In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's diseasewho had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximabthen infliximab, or infliximabthen CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximabat weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index(CDAI) from baseline to week 6. A non-inferiority margin of −20% was set (CT-P13 was non-inferior to infliximabif the lower limit of the two-sided 95% CI for the treatment difference was greater than −20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. Findings Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13–CT-P13 group and 55 to the CT-P13– infliximabgroup) and 109 to initiate infliximab(54 to the infliximab–infliximabgroup and 55 to the infliximab–CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab(81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference −4·9% [95% CI −16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13–CT-P13 group, 34 [62%] in the CT-P13– infliximabgroup, 37 [69%] in the infliximab–infliximabgroup, and 40 [73%] in the infliximab–CT-P13 group). Interpretation This study showed non-inferiority of CT-P13 to infliximabin patients with active Crohn's disease. BiosimilarCT-P13 could be a new option for the treatment of active Crohn's disease. Funding Celltrion, Pfizer.