Issue 05

Clinical Question

Can patients with immune-mediated inflammatory disorders on a stable dose of infliximab (IFX) for at least 6 months switch to the IFX biosimilar CT-P13 without significant disease worsening within one year?

Editor’s Bottom Line

Switching seems to be both effective and well tolerated. Although the risk difference in Crohn’s disease (CD) patients approached the non-inferiority margin, the trial was not powered for subgroup analysis.

Reference

Jørgensen KK, Olsen IC, Goll GL, et al; NOR-SWITCH study group. 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. Lancet. 2017 Jun 10;389(10086):2304–16. https://www.ncbi.nlm.nih.gov/pubmed/28502609

Synopsis

Adult patients taking a stable dose of originator IFX for more than 6 months were randomized 1:1 to originator IFX or biosimilar CT-P13 at the same doses and infusion intervals. The primary outcome was disease worsening during the 52 week follow-up specific for each disease type; for CD it was a 4 point increase in baseline Harvey-Bradshaw Index (HBI) and a score of ≥7 points and for ulcerative colitis (UC) it was >3 points increase from baseline partial Mayo and a total score of ≥5 points. For non-inferiority it was required 90% confidence that the upper limit of the two-sided 95% confidence interval excluded a risk difference of 15% in favour of originator IFX.

Of the 408 per protocol patients included, there were 78 (32%) CD and 47 (20%) UC patients in the originator IFX cohort (n=241) and 77 (32%) CD and 46 (19%) UC patients in the biosimilar CT-P13 cohort (n=240). The remaining patients had spondyloarthritis, rheumatoid or psoriatic arthritis, and psoriasis. Overall, disease worsening occurred in 26% and 30% of patients in the originator IFX and biosimilar CT-P13 cohorts, respectively (adjusted risk difference of -4.4% 95% CI: -12.7 to 3.9%). Specifically, for CD and UC, the risk differences were -14.3% (-29.3 to 0.7) and -2.6% (-15.2 to 0.7), respectively. IBD-specific secondary outcomes (e.g., fecal calprotectin, HBI, and partial Mayo) were similar between the cohorts. No significant differences for adverse or severe adverse events were noted between originator IFX and biosimilar CT-P13.

Details

Study Design: Prospective double-blind randomized non-inferiority clinical trial
Funding: Norwegian Ministry of Health and Care Services
Allocation: Computer block randomisation stratified by diagnosis with fixed block size of 6
Setting: 40 centres in 25 hospitals, Norway
Level of Evidence: 1b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.