Background: TNF-inhibitors have improved treatment of Crohn's disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and chronic plaque psoriasis (Ps). The aim of the Nor-Switch study was to examine switching from originator to biosimilar infliximab regarding efficacy, safety and immunogenicity.
Methods: The study was designed as a 52-week randomised, double-blind, non-inferiority trial. Patients with a diagnosis of CD, UC, SpA, RA, PsA or Ps on stable maintenance treatment with the originator infliximab (Remicade®, INX) were randomized 1:1 to either continued INX or switch to biosimilar infliximab (Remsima®, CT-P13). The primary endpoint was disease worsening according to disease activity indices during follow-up.
Results: In total, 481 patients at 40 Norwegian study centres were randomised, with 202/206 patients in the INX/CT-P13 arms (Per Protocol Set). There were 129 (32%) and 75 (18%) patients with CD and UC. Overall disease worsening occurred in 26.2% and 29.6% of patients in the INX and CT-P13 arms, respectively, and the 95% confidence interval (CI) of the adjusted difference was within the pre-specified non-inferiority margin (−4.4; 95% CI −12.7, 3.9%). In CD, disease worsening occurred in 21.2% and 36.5% (CI −29.3 to 0.7%) and in UC 9.1% and 9% (CI −15.2, 10.0%). The CI for CD was close to non-inferiority for CT-P13, but disease specific analyses were pre-specified as exploratory and NOR-SWITCH was not powered for demonstrating non-inferiority in the single diagnoses.
The baseline characteristics in CD and UC showed no difference between treatment arms regarding previous biologic therapy, use of immunosuppressives, trough drug levels, disease duration, distribution, behaviour and activity (Harvey-Bradshaw Index (HBI) and Partial Mayo Score (PMS)), bowel surgery, smoking, CRP, fecal calprotectin, and EQ-5D.
Changes in parameters from baseline to study end showed similarity between arms (adjusted difference, (95% CI)) in CD and UC, respectively, regarding CRP (−0.07 (−0.17, 0.04) and −0.04 (−0.18, 0.10)), fecal calprotectin (−0.08 (−0.27, 0.10) and 0.21 (−0.03, 0.44)), HBI (−0.41 (−1.14, 0.33)), PMS (0.14 (−0.30, 0.59)), HBI and PMS remission. Changes in Patient's and Phycician's global assessment of disease activity showed some larger improvement in the INX compared to the CT-P13 arm in the CD group (−0.65 (−1.22, −0.07) and −0.42 (−0.85, 0.001)). Comparable results were also seen for through serum levels, presence of anti-drug antibodies and reported adverse events.
Conclusions: Explorative subgroup analyses of CD and UC in the Nor-Switch study showed similarity between patients treated with INX and CT-P13 with regard to efficacy, safety and immunogenicity.