BIOSIMILAR INFLIXIMAB (CT-P13) IS NOT INFERIOR TO ORIGINATOR INFLIXIMAB: EXPLORATIVE SUBGROUP-ANALYSES IN CROHN’S DISEASE AND ULCERATIVE COLITIS IN THE NOR-SWITCH EXTENSION TRIAL

INTRODUCTION: TNF-inhibitors have improved treatment of Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis, spondyloarthritis, psoriatic arthritis and chronic plaque psoriasis. The NOR-SWITCH 52-week, double blind, non-inferiority trial showed that switching from originator (Remicade®, IFX) to biosimilar (Remsima®, CT-P13) infliximab was not inferior to continued treatment with IFX regarding efficacy, safety and immunogenicity. Though explorative subgroup analyses in CD demonstrated an estimated difference close to the non-inferiority margin for CT-P13, the trial was not powered for demonstrating non-inferiority in the individual diagnoses. AIMS & METHODS: In the 26-week open label NOR-SWITCH EXTENSION trial treatment efficacy, safety and immunogenicity were assessed in patients on CT-P13 throughout the 78-week study period (maintenance group) compared to patients switched from IFX to CT-P13 at week 52 (switch group). The primary endpoint was disease worsening during follow-up according to disease-specific indices. Explorative subgroup analyses were performed to examine disease worsening within each of the six diagnoses. RESULTS: In total, 380 of 451 patients in the main trial entered the extension phase (Full Analysis Set). Overall disease worsening occurred in 16.8% (32/190) and 11.6% (20/173) in the maintenance and switch arms, respectively, and the 95% confidence interval (CI) of the adjusted difference was within the pre-specified 15% non-inferiority margin (−5.9%; 95% CI −12.9,1.1) (Per Protocol Set, PPS). The incidence of adverse events and anti-drug antibodies (ADAb) were comparable between arms. In CD, disease worsening occurred in 20.6% and 13.1% (−7.9%; 95% CI −21, 5.2) and in UC in 15.4% and 2.9% (−12.4%; 95% CI −25, 0.1) of patients in the maintenance and switch group, respectively (PPS) (table). These results were within the non-inferiority margin. The baseline characteristics in CD and UC when entering the extension trial at week 52 showed no difference between arms regarding age, gender, previous biologic therapy, use of immunosuppressants, trough drug levels, disease duration, extension, behaviour and activity (Harvey-Bradshaw Index (HBI) and Partial Mayo Score (PMS)), bowel surgery, smoking, CRP, faecal calprotectin, and EQ-5D. Changes in disease measures from baseline to study end in CD and UC, respectively, showed similarity between treatment arms regarding HBI, PMS, HBI and PMS remission, CRP, faecal calprotectin and Patient’s and Physician’s global assessment of disease activity (PPS)(table). Comparable results were also seen for reported adverse events, trough serum levels and presence of ADAb. CONCLUSION: The open label NOR-SWITCH EXTENSION trial did not show any difference between patients who maintained CT-P13 vs. those who switched from IFX to CT-P13. In the same way, explorative subgroup analyses of CD and UC showed similarity between groups with regard to efficacy, safety and immunogenicity.