Recently, biosimilar tumour necrosis factor (TNF) antagonists have become available and are being increasingly used in treating inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC). The first infliximab biosimilar to receive approval was CT-P13 (Remsima) based on data from rheumatoid arthritis and ankylosing spondylitis, followed by extrapolation to other indications of originator infliximab (Remicade). The second infliximab biosimilar, SB2 (Flixabi), received authorization based on a pharmacokinetic study in healthy volunteers and a study in rheumatoid arthritis .
With encouraging efficacy and safety data for a single switch from originator to biosimilar [2, 3], reimbursement policies have changed, which often led to switches between biosimilars or multiple successive switches between biosimilars – situations for which little data exist. To address this knowledge gap, a prospective multicentre cohort study was performed to evaluate the effectiveness and safety of multiple successive switching from originator to a second infliximab biosimilar compared to a single switch from originator to CT-P13 and a single switch between CT-P13 and SB2 in patients with IBD .
In the two participating non-academic hospitals, adult patients with IBD underwent a switch from originator infliximab to CT-P13 from August 2015 onwards as part of routine care. This was followed by a routine switch for economic reasons from CT-P13 to SB2 from July 2018 onwards. The switching procedures yielded three groups: patients who successively switched from originator infliximab to CT-P13 and finally to SB2, patients who switched from originator infliximab to CT-P13 and patients who switched from CT-P13 to SB2.
Patients were followed according to protocolized switch pathways with C-reactive protein (CRP) and faecal calprotectin (FC) measurements prior to the index switch, and 4 and 12 months after the index switch. The primary efficacy outcome was clinical remission per physician’s assessment without concomitant steroid therapy 12 months since the index switch. Secondary efficacy endpoints included CRP remission defined as CRP < 5 mg/L, FC remission defined as FC < 250 mg/kg and time to treatment discontinuation.
A total of 176 patients were included in the study (69 switching from the originator to CT P13 and to SB2, 80 switching from CT-P13 to SB2, 27 from the originator to CT P13). At 12 months after the index switch 76.9% (40/52) of patients successively switching from the originator to CT-P13 and then to SB2, 65.7% (46/70) of patients switching from CT-P13 to SB2 and 76.9% (20/26) of patients switching from the originator to CT-P13 were in clinical remission. There were no significant differences in the rate of clinical, CRP or FC remission at 12 months, although rates were numerically lower in patients switching from CT-P13 to SB2. Infusion reactions occurred in 3.8% (3/80) of patients switching from CT-P13 to SB2, no infusion reactions were recorded in the other two groups. At 12 months, the estimated treatment persistence was 85.0% for patients successively switching from originator to CT-P13 to SB2, 87.0% for patients switching from CT-P13 to SB2 and 70.1% for patients switching from the originator to CT-P13.
Similar rates of clinical and biochemical remission at 12 months were observed in patients undergoing multiple successive switches, a single switch between biosimilars or a single switch from the originator to CT-P13. No unexpected adverse events or de novo immunogenicity were observed in patients after multiple successive switches. These findings suggest that multiple successive switches from originator infliximab to biosimilars are effective and safe, particularly if patients are in remission at the time of the switch. These results were further corroborated in two additional cohorts [5, 6].
Conflict of interest
The authors of the research paper  reported conflict of interest, including having received consultancy and/or speakers fees from pharmaceutical companies and having served on advisory boards or as an advisor for pharmaceutical companies. For full details of the authors’ conflict of interest, see the research paper .
Abstracted by Dr Jurij Hanzel of the Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, The Netherlands and the Medical Faculty, University of Ljubljana, Department of Gastroenterology, UMC Ljubljana, Ljubljana, Slovenia.
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BSG guidance recommends switching to biosimilar infliximab
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Switching from originator infliximab to CT-P13: real-world data with 24 months of follow up
Is switching to biosimilar infliximab safe?
1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Oct 1]. Available from: www.gabionline.net/biosimilars/general/biosimilars-approved-in-europe
2. Jorgensen KK, Olsen IC, Goll GL, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389(10086):2304-16.
3. Ye BD, Pesegova M, Alexeeva O, et al. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study. Lancet. 2019;393(10182):1699-707.
4. Hanzel J, Jansen JM, Ter Steege RWF, et al. Multiple Switches from the originator infliximab to biosimilars is effective and safe in inflammatory bowel disease: a prospective multicenter cohort study. Inflamm Bowel Dis. 2021;izab099.
5. Luber RP, O'Neill R, Singh S, et al. An observational study of switching infliximab biosimilar: no adverse impact on inflammatory bowel disease control or drug levels with first or second switch. Aliment Pharmacol Ther. 2021.
6. Trystram N, Abitbol V, Tannoury J, et al. Outcomes after double switching from originator Infliximab to biosimilar CT-P13 and biosimilar SB2 in patients with inflammatory bowel disease: a 12-month prospective cohort study. Aliment Pharmacol Ther. 2021;53(8):887-99.
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