Treatment Persistence, Safety After Switching to Infliximab Biosimilars in Canadians With IBD

A retrospective study of a mandatory nonmedical switch from the infliximab reference product (Remicade) to biosimilars CT-P13 (Inflectra) or SB2 (Renflexis) found no significant differences in rates of treatment persistence, loss of response, or adverse events in patients with inflammatory bowel disease (IBD) on maintenance therapy 1 year post-switch.

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Infliximab is a monoclonal antibody targeting tumor necrosis factor-α, a pro-inflammatory cytokine involved in several immune-mediated inflammatory diseases, including Crohn disease (CD) and ulcerative colitis (UC), collectively called IBD. In Canada, the reference product was approved for use in CD in 2001 and UC in 2006. The first biosimilars initiative in Canada was launched in the province of British Columbia in 2019, beginning a mandatory switch from the reference infliximab to a biosimilar, either CT-P13 or SB2, for all publicly funded patients receiving the reference product.

The investigators aimed to evaluate real-world clinical outcomes following the mandatory switch with their retrospective observational study that analyzed data stable IBD patients from the IBD Centre of British Columbia who underwent a nonmedical infliximab switch and a control group who remained on the reference product. The primary outcome was treatment persistence 12 months post-switch, and secondary outcomes included loss of response, adverse events, and immunogenicity.

The study included 364 patients, 265 who underwent a switch and 99 who remained on infliximab therapy with the reference product. The 2 groups of patients displayed similar demographic characteristics, the authors said, with no statistically significant differences in disease characteristics, except that the switch group was somewhat younger at the time of diagnosis (26 vs 23 years). Also, the control group had a shorter mean duration on the reference product prior to the beginning to the mandatory switch program compared to those who switched (70 vs 43 months). Approximately 41% of the patients who switched continued therapy on CT-P13, and the rest continued on SB2.

More than 90% of patients in both groups remained on infliximab treatment at 12 months

At 12 (+/-2) months, there was no significant difference in treatment persistence between patients who switched to biosimilars (90%) and those who remained on the reference product (95%). Of patients who switched to infliximab biosimilars 92% of patients with CD and 87% of patients with UC were still undergoing infliximab treatment at 1 year, compared to 95% and 91% of CD and UC patients who remained on the reference product.

Reasons for discontinuation of therapy included loss of response in 4% and 5% of patients on biosimilars and the reference product, immunogenicity in approximately 1% of each group, and adverse effects in 1% and 2% of patients. The authors noted there were no significant differences between groups in reasons for discontinuation between groups.

Discontinuation and the nocebo effect

Eight patients in the biosimilar group discontinued treatment following an adverse reaction to infliximab, 2 patients on SB2 (1.82%) and 6 on CT-P13 (2.56%). Two patients in the reference product group (1.01%) discontinued treatment due to adverse effects. There were no significant differences between groups.

The investigators commented that the frequencies of treatment discontinuation observed in their study were lower than some previous studies that reported post-switch discontinuation rates as high as 22%. They wrote that authors of those studies attributed the discontinuation to the nocebo effect, and “our centre employs clinical IBD nurses who assisted in counselling patients regarding the switch, which may have mitigated the nocebo effect previously reported.” However, their analysis with adjustment for potential confounders found a non-significant increase in the likelihood of treatment discontinuation in switchers compared to the control group (HR, 2.11; 95% CI, 0.57-1.04; P = .148), which could have reflected the nocebo effect. They wrote, “our study was also underpowered to comment on the observed numerical difference in adverse event rates.”

The authors concluded the nonmedical switch of patients with IBD on infliximab therapy in British Columbia demonstrated “similar clinical outcomes” between patients who did and did not switch, and their results “support the existing clinical data on infliximab biosimilar switching from Europe and Asia, which can inform future practice guidelines and reassure healthcare providers about the safety and efficacy of biosimilar switching in IBD.”

Some limitations cited were an inability to objectively determine remission at the time of switching and inability to control for factors such as objective disease activity, serum inflammatory markers, and previous immunogenicity in their analyses. Also, the authors said they were unable to compare serum drug persistence because of the small number of patients with therapeutic drug monitoring data available.

Reference

Hoang TT, Reid J, Galorport C, Bressler B, Leung Y, Rosenfeld G. Outcomes of a mandatory non-medical switch of infliximab to a biosimilar for inflammatory bowel disease in British Columbia, Canada. J Can Assoc Gastroenterol. 2024;7(4):299-305. doi:10.1093/jcag/gwae011