Switching Patients With IBD to Infliximab, Adalimumab Biosimilars Did Not Impact Efficacy

The mandatory switching policies that have been established in most Canadian provinces motivated researchers to systematically review the real-world evidence on safety and effectiveness of switching from tumor necrosis factor (TNF)-α inhibitor originators to biosimilars in inflammatory bowel disease (IBD).

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In real-world studies on infliximab, 75% of patients were in clinical remission at the time of switching, and 75% of those who switched to a biosimilar were in clinical remission at a median of 12 months of follow-up. Studies on adalimumab reported 86% were in clinical remission at the time of switch, and 82% at a median of 6 months of follow-up. The authors said their findings “should be reassuring to patients and clinicians,” as no significant differences in clinical effectiveness or serious adverse events between originators and biosimilars were reported in the reviewed studies.

Crohn disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract and are collectively known as IBD. Biologic therapies account for a “significant burden” of the cost associated with IBD to health care systems, according to the authors.

In Canada, they said sales of biologics increased from $3.3 billion to $10.0 billion over the last 10 years. To curb costs, the first mandatory switch policy was established for infliximab in British Columbia in 2019. Several other provinces followed, and the rest are expected to soon have mandatory switch policies in place for all patients with IBD receiving infliximab or adalimumab.

The authors noted that biosimilars now account for 94% of the infliximab market share in British Columbia. As nationwide biosimilar switching is expected to soon be complete for IBD in Canada, the authors aimed to review the real-world evidence.

The systematic review of 43 real-world observational studies included 7462 adult patients with IBD, 70% of whom had CD and 30% had UC, who had switched from an anti-TNF originator to a biosimilar (n = 32 studies on infliximab; n = 11 studies on adalimumab). Infliximab biosimilars included CT-P13, SB2, or both, and 7 studies included data on multiple switches. Adalimumab biosimilars studied included AB501, SB5, ABP501, GP2017, and MSB11022.

Ten studies investigated clinical remission within the first 12 months after switching to a biosimilar, 7 on infliximab and 3 on adalimumab. Patients were treated with reference infliximab (Remicade) for a median of 40 months prior to switching. Ninety-two percent of patients were in remission at the time of switch and 88% were in remission at a median of 5 months after switching, a difference that was not statistically significant. Patients were treated with reference adalimumab (Humira) for a median of 41 months prior to switching, and 86% in clinical remission at the time of switch compared to 82% at 6 months of follow-up.

Thirteen studies investigated clinical remission at 12 months or longer following switching, 11 on infliximab and 2 on adalimumab. Patients were treated with the infliximab originator for a median of 53 months before switching, and 75% were in remission at time of switch and at a median of 12 months after switching. These adalimumab studies did not report on the duration of treatment with the originator, and only 1 of the 2 studies reported clinical remission rate at baseline (100%). Overall, 77% were in clinical remission 12 months after switching.

In studies of either infliximab or adalimumab biosimilars that reported clinical parameters, no significant differences between time of switch and final follow-up were reported for mean or median values of C-reactive protein, fecal calprotectin, or disease scores such as Harvey Bradshaw Index or Mayo score.

Loss of response was reported in 13 studies on infliximab and 2 studies on adalimumab. Patients were treated with the reference infliximab for a median of 45 months, and loss of response occurred in 17.5% of patients at a median follow-up of 28 weeks. In adalimumab studies, 15% of patients experienced loss of response after a median follow-up of 52 weeks. The authors commented that these rates of loss of response “are not dissimilar to data from originator studies.”

Drug persistence was reported in 19 studies on infliximab and 7 studies on adalimumab. Patients had been treated with the infliximab originator for a median of 53 months prior to switching, and 29% were also receiving thiopurines or methotrexate. At a median follow-up of 12 months, the rate of persistence with infliximab biosimilar treatment across all studies was 84%. Patients receiving adalimumab had been treated with the reference product for a median of 33 months prior to switching, and 15% were receiving concomitant immunomodulatory therapies. At a median follow-up of 12 months, 81% of patients remained on adalimumab biosimilar therapy.

The reviewers concluded that although ongoing vigilance of switching to anti-TNF biosimilar therapies in IBD will be necessary, “these data are reassuring to both patients and clinicians and will significantly help to reduce health-care costs across Canada.” They added that appropriate counseling, assessment of disease activity and any side effects, and careful follow-up after switching “will help to ensure optimal patient care while helping to achieve the financial benefits of a mandated switch policy.”

Reference

Meade S, Squirell E, Hoang TT, Chow J, Rosenfeld G. An update on anti-TNF biosimilar switching-real-world clinical effectiveness and safety. J Can Assoc Gastroenterol. 2023;25;7(1):30-45. doi:10.1093/jcag/gwad027