Switching from infliximab to biosimilar in inflammatory bowel disease: overview of the literature and perspective

Abstract

Background: Biological therapy has revolutionized the treatment of inflammatory bowel disease (IBD). After the expiration of patents for biological innovator products, development of biosimilars increased. CT-P13 was the first biosimilar approved for the same indications as the reference product; however, the approval was based on extrapolated data from rheumatoid arthritis and ankylosing spondylitis. Our aim was to review clinical studies about switching from originator infliximab (IFX-O) to biosimilar infliximab (IXF-B) in IBD, focusing on recently published data and the future of biosimilars. Methods: The PubMed database was searched for original articles published up to 1 December 2018 reporting data on IFX-B in IBD. Results: A total of 29 studies assessing switching from IFX-O to IFX-B, 14 assessing induction therapy with IFX-B were found. Efficacy, safety and immunogenicity were discussed. Studies confirm that CT-P13 is safe and equally efficient as the reference product for both induction and maintenance therapy; and that switching from the reference product to biosimilar is non-inferior to continuous biosimilar use. However, efficacy and safety data on Flixabi (SB2) in IBD patients is lacking. Conclusion: Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching and cross-switching among biosimilars in IBD patients.

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

“…For extrapolation to be permitted, biosimilarity must have been demonstrated in in vitro, nonclinical, and clinical studies, and the rationale for extrapolation must be scientifically justifiable [3]. Today, approval of CT-P13 in IBD is also supported by real-world evidence and clinical trial data [34,[120][121][122][123], including from the randomized, double-blind, noninferiority phase IV NOR-SWITCH study [120] and a Hungarian prospective observational cohort study [124]. To our knowledge, no published clinical trials evaluating the approved adalimumab biosimilars ABP 501, BI 695501, or SB5 in IBD, or real-world evidence for other infliximab biosimilars exist.…”

The Importance of Countering Biosimilar Disparagement and Misinformation

“…Incorrect or misleading conclusions about biosimilars have been published in scientific literature, enabling others to quote the misleading conclusions as fact and creating a false narrative. An article on the ethics of biosimilars [ 33 ] cited three literature reviews [ 34 – 36 ] to conclude that the safety and efficacy of switching once from a reference product to a biosimilar is still controversial, and therefore physicians are ethically obligated to inform prospective biosimilar recipients of this “fact.” However, a close examination of the three reviews found that none of them identified any specific safety or lack of efficacy concern related to switching once from a reference biologic to a biosimilar. Another recent review of 178 switching studies also concluded that for the products studied, a single switch is not intrinsically linked to an increase in immunogenicity, safety, or efficacy issues [ 37 ].…”

The Law and Ethics of Switching from Biologic to Biosimilar in Canada

“…There is some concern that switching a patient currently in remission on a biologic to a biosimilar could potentially have uncertain or adverse results ( 11 , 32 ), especially in cases of comorbidity or other complex patient or disease-specific characteristics ( 33 ). Two 2018 meta-analyses of research into clinical outcomes of switching to biosimilars came to different conclusions regarding safety: one concluded that “there are important evidence gaps around the safety of switching” ( 34 ), while the other claimed their results provided reassurance that “the risk of immunogenicity-related safety concerns or diminished efficacy is unchanged after switching from a reference biologic to a biosimilar medicine.” ( 35 ) And another review of 29 studies concerning switching for patients with inflammatory bowel disease concluded that “scientific and clinical evidence is lacking regarding reverse switching, multiple switching and cross-switching among biosimilars” ( 36 ). Given such inconsistencies, and since many patients in remission on a reference biologic are likely to have experienced multiple failed treatments in the past, some patients may want to remain on the same drug ( 37 ).…”