Disease Activity, Safety Remain Following Switch From Infliximab Biosimilar to Remicade in IBD

Switching back from infliximab biosimilar SB2 to reference infliximab (Remicade) did not affect clinical disease activity or safety in inflammatory bowel disease (IBD), according to a prospective cohort study.

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According to the investigators, “the initial and the reverse switch had no relevant impact on the course of disease and additionally no safety issues occurred.”

The reference anti-tumor necrosis factor (TNF) antibody infliximab was first approved to treat IBD—Crohn disease (CD) and ulcerative colitis (UC)—in 1998. Biologics account for a large proportion of costs associated with IBD, authors of the study noted. In 2013, the European Medicines Agency approved CT-P13 as the first infliximab biosimilar, and SB2 (Flixabi/Renflexis), was approved by the European Medicines Agency in 2016 and by the FDA in 2017.

Real-world studies and randomized controlled trials have shown similar efficacy, safety, and immunogenicity of infliximab biosimilars to the originator in IBD. Switching from the reference infliximab to a biosimilar for economic reasons is now part of routine care during treatment for IBD, the authors said, and data on multiple switches, including reverse switching to the originator, is scarce.

In the prospective, single-center, observational cohort study, patients with IBD receiving the infliximab reference product were switched to biosimilar SB2 and followed for 96 weeks. After, they switched back to the originator and were followed for 48 weeks. Analyzing the 80-week period following the switch to SB2, they found “switch did not impact the primary outcome measure clinical disease activity at week 80.” They then followed the same cohort for another 16 weeks, then switched the patients back to the originator and followed them for another 48 weeks.

The primary outcome of the study was clinical disease activity (Harvey-Bradshaw Index, HBI, for CD, partial Mayo score, pMS, for UC) at 24 weeks and 48 weeks, and secondary outcomes included C-reactive protein, trough levels, anti-drug antibodies, and safety.

Patients were followed for a median of 56 weeks after the reverse switch. The median HBI was 2 (IQR, 1-4) at baseline and 2 (IQR, 1-4) at week 48. Median pMS was 1 (IQR, 0-1) at baseline and 0.5 (IQR, 0-1) at week 48. Neither mean change was statistically significant.At baseline, 80% of patients were in remission, and 82% were in remission at week 48. No patients experienced severe disease activity, and no clinically relevant changes in disease activity were observed.

Median C-reactive protein (CRP) levels were 2.0 mg/L (IQR, 1.0-4.1) at baseline and 2.4 mg/L (IQR, 1.1-5.2) at week 48, resulting in a mean (SD) change of 1.7 (5.8). The changes from baseline to week 48 were not significant in CD or UC. The authors wrote, “the median CRP levels remained below the threshold of 5 mg/l, which was considered to be normal. “

Median trough levels were 7.2 µg/ml (IQR, 3.8-19.3) at baseline and 5.5 µg/ml (IQR, 3.5-13.1) at week 48, for a mean change of –1.0 (7.4), which was not statistically significant in CD or UC. Trough levels within the therapeutic range were found in 31% of patients at baseline, 33% at week 24, and 37% at week 48.

Antidrug antibodies (ADA) were developed by 3.4% (n = 3 patients) during the reverse switch period. At baseline, 9% of patients were positive for ADAs, followed by 6% at week 24 and 8% at week 48. Most patients (87%) did not develop ADAs during the study.

Dosing of infliximab at week 48 compared to baseline was stable for 40% of patients, lower for 39% and higher for 21% of patients. The treatment schedule was unchanged for 67% of patients at week 48, shorter intervals for 11% and longer intervals for 22%. Regression models were used to analyze changes in trough levels, CRP, and 8-week dosing from one year before to one year after the reverse switch. There were no statistically significant changes in these three parameters.

Safety was “consistent with previous studies,” the investigators said. There were 66 adverse events (AEs) in 46 patients (48%). Seven AEs were considered serious, including 1 metastasized malignancy, 1 bowel resection due to an inflammatory stenosis, 2 hospitalizations, 1 instance of sepsis, and 1 traumatic subarachnoid haemorrhage. Most AEs (42/66) were not considered to be associated with treatment.

Four of the 95 patients discontinued treatment due to safety concerns, including relapsing infusion reactions for 2 patients, 1 malignancy, and 1 instance of sepsis.The overall rate of discontinuation of therapy was 14.7%. Of patients who discontinued treatment, 30% were ADA positive and 70% had trough levels below the therapeutic range.

The authors acknowledged the limited sample size and lack of objective clinical activity data, and lack of a control group continuing SB2 as limitations of their study. They also noted selection bias as only patients with a long-term response to infliximab prior to the reverse switch were included, adding that the timing of switching “might potentially be more favourable in patients who have stable disease” compared to patients newer to infliximab therapy.

The investigators concluded that reverse switching did not affect effectiveness, immunogenicity, or safety of infliximab therapy in their study, and said their findings support the practice of switching between the infliximab reference product and its biosimilars.

Reference

Fischer S, Donhauser M, Cohnen S, et al. Reverse switching from the biosimilar SB2 to the originator infliximab in previously switched patients with inflammatory bowel diseases: results of a prospective long-term cohort study. Therap Adv Gastroenterol. 2024;17. doi:10.1177/17562848241301887