Background: Data regarding multiple switches including reverse switching between infliximab and its biosimilars are scarce in the field of inflammatory bowel diseases (IBD).
Objectives: We investigated the clinical effectiveness as primary outcome measure after repeated switches. Secondary endpoints included C-reactive protein (CRP) levels, immunogenicity (trough levels (TL); anti-drug antibodies (ADA), safety and drug persistence.
Design: This study is a prospective, single-centre, observational cohort study. IBD patients receiving originator infliximab were switched to biosimilar SB2 and then reverse switched after 96 weeks and followed up for another 48 weeks.
Methods: Clinical disease activity (Harvey-Bradshaw-index (HBI) in Crohn's disease (CD), partial Mayo score (pMS) in ulcerative colitis (UC)), CRP, TL, ADA, therapy-discontinuations and (serious) adverse events ((S)AE)) were monitored throughout the study.
Results: Ninety-five patients (60 CD, 38 female) were enrolled. The median HBI was 2 (interquartile range (IQR) 1-4) at baseline and 2 (1-4) at week 48, resulting in a mean intra-individual change of 0.0 (standard deviation (SD) 1.5). The median pMS was 1 (IQR 0-1) at baseline and 0.5 (0-1) at week 48 resulting in a mean intra-individual change of 0.0 (SD 0.8). Clinical remission was achieved in 80% at baseline and 82% at week 48. Median CRP 2.0 mg/l (IQR 1.0-4.1) at baseline and 2.4 mg/l (1.1-5.2) at week 48 resulted in a mean change of 1.7 (SD 5.8) and no significant differences in CD (p = 0.3) and UC (p = 0.9). Median TL were 7.2 µg/ml (IQR 3.8-19.3) at baseline and 5.5 µg/ml (3.5-13.1) at week 48, resulting in a mean change of -1.0 (SD 7.4) with no statistical significance (CD p = 0.26, UC p = 0.41). De-novo-ADA were developed by 3.4%. The discontinuation rate was 14.7%. Safety signals were consistent with previous studies.
Conclusion: Reverse switching had no impact on efficacy of infliximab therapy in our cohort of IBD patients. The switch didn't influence immunogenicity or safety of therapy.
Keywords: IBD; SB2; biological; biosimilar; infliximab; multiple switches; reverse switch; switch.
A clinical study investigating the interchangeability between infliximab, a previously patented biotechnological produced drug (biological) and its successor product biosimilar SB2, which is highly similar to the existing reference product, in the treatment of patients with inflammatory bowel diseases Why was the study done? Biological drugs (like infliximab) are produced using various methods under the involvement of biotechnology. In contrary to generic drugs, due to their complex structure, biosimilars are not exactly the same molecule as the original substance. After the introduction of biosimilars, which are mostly less expensive than the original product, concerns were raised regarding the interchangeability of these substances. This study was conducted to investigate potential changes in efficacy and safety after multiple, so called switches (from the original product to its biosimilar and back). What did the researchers do? The research team switched a group of 95 patients diagnosed with inflammatory bowel disease and therefore treated with the original biologic drug infliximab to the biosimilar SB2, reverse switched them back to the original drug after 96 weeks and observed the patients for another 48 weeks. During the observational phase the disease activity, drug levels and potential side effects were monitored. What did the researchers find? The initial and the reverse switch had no relevant impact on the course of disease and additionally no safety issues occurred. During the 48 weeks observational period, 14.7% of patients discontinued therapy, which was not out of the expected range. Most potential side effects were not considered to be therapy-associated and only 4 of 95 patients discontinued treatment due to safety concerns. The drug levels remained stable during the switches. What do the findings mean? In this study, the research team found no impact of multiple switches on the disease activity in inflammatory bowel disease patients and moreover no safety issues. These findings support the practice of switching between the biologic originator substance infliximab and its biosimilars.
© The Author(s), 2024.