Real-World Evidence of Clinical Outcomes of the Use of the Adalimumab Biosimilar SB5 in Rheumatic and Gastrointestinal Immune-Mediated Inflammatory Diseases: 12-Month Data from the PERFUSE Study.

Background: There is a need for published data on real-world use of SB5, an adalimumab (ADL) biosimilar approved in Europe in 2017, on the basis of evidence from pre-clinical and analytic data as well as phase I and III clinical studies demonstrating equivalent efficacy and comparable pharmacokinetics, safety and immunogenicity profiles as the reference ADL.
Objectives: The purpose of this study was to estimate patient persistence on SB5 at 12 months post-initiation using clinical and healthcare claims data from the French Système National des Données de Santé (national healthcare claims database, SNDS) in addressing data gaps.
Methods: PERFUSE is a 12-month, observational, multi-centre cohort study of patients with rheumatic or gastrointestinal immune-mediated inflammatory diseases (IMIDs) who initiated routine SB5 treatment between October 2018 and October 2020, either as their first ADL (naïve) or transitioning from another ADL (switched). Clinical data, including disease activity scores, C-reactive protein levels, and dosing information, were collected as available from patient records captured during routine visits to specialist physicians. Persistence data were supplemented with data from the French national healthcare claims database (SNDS). Analyses of clinical data were descriptive, while persistence was assessed using a Kaplan-Meier survival analysis.
Results: Overall, 911 patients were included: 507 from rheumatology centres [116 with rheumatoid arthritis (RA), 78 psoriatic arthritis (PsA), and 313 ankylosing spondylitis (AS)] and 404 from gastroenterology centres [316 with Crohn's disease (CD) and 88 ulcerative colitis (UC)]. Among naïve patients, 12-month remission/low activity rates were 58% for RA, 66% for PsA, 59% for AS, 94% for CD, and 85% for UC, increasing significantly from baseline for all indications (p < 0.05). Switched patients' remission rates remained stable between baseline and month 12 (M12) for all indications (p > 0.05). Persistence (95% CI) at M12 among naïve patients was 59% (46.5, 68.8) for RA, 65% (49.7, 77.1) for PsA, 56% (48.3, 62.6) for AS, 70% (63.0, 75.7) for CD, and 42% (30.7, 53.1) for UC, compared to 60% (42.7, 73.7) for RA, 57% (37.3, 72.1) for PsA, 55% (45.8, 64.0) for AS, 63% (53.4, 71.7) for CD, and 56% (27.2, 77.6) for UC among switched patients. No significant differences were observed between naïve and switched patients (p > 0.05). SNDS pairing provided information on 68 of the 132 patients (52%) who were lost to follow-up in the clinical database, of whom 57 (84%) were confirmed persistent at M12 and 11 (16%) non-persistent. Primary treatment failure (naïve patients) and patient decision (switched patients) were the most common reasons stated for treatment discontinuation.
Conclusions: SB5 provides clinically effective treatment of both gastrointestinal and rheumatic IMIDs for naïve and switched patients, with no loss of control observed when switching. Persistence was comparable between naïve and switched populations, though the reasons for non-persistence differed.
Trial Registry: Trial registration number: Clinical Trials identifier NCT03662919. Trial registration date: 10 September 2018.
Competing Interests: Declarations. Funding: This study was sponsored by Biogen Int GmbH (Baar, Switzerland). Funding was provided by Biogen. Open access fees were sponsored by Biogen Int GmbH (Baar, Switzerland). Conflict of interest: Bruno Fautrel: received speaker/consulting fees from AbbVie, Biogen, Boehringer Ingelheim, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sobi and UCB, and grant/research support from AbbVie, MSD and Pfizer. Yoram Bouhnik: received consultancy and/or speaker fees from AbbVie, Biogaran, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoly Spindler, Merck, Merck Sharp & Dohme, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB and Vifor Pharma. Carine Salliot: received consultancy and/or speaker fees from Novartis, Roche-Chugai, Pfizer and Galapagos, and grant/research support from Roche-Chugai and Novartis. Frank Carbonnel: received speaker fees from Abbvie, Astra, Biocodex, Biogen, Ferring, Janssen, MSD, Pfizer, Pileje, Takeda, Tillotts; and is a member of advisory boards for Amgen, Arena, BMS, Celltrion, Enterome, Ferring, Janssen, Medtronic, Pfizer, Pharmacosmos, Roche and Tillotts. Mathurin Fumery: received consultancy and/or speaker fees from AbbVie, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Takeda, Tillots and Celgene. Chirstophe Bernardeau: nothing to disclose with respect to their contributions to this work. Yves Maugars: nothing to disclose with respect to their contributions to this work. Mathurin Flamant: received consultancy and/or speaker fees from AbbVie, Amgen, Biogen, Ferring, Janssen, Mayoly Spindler, Merck Sharp & Dohme, Pfizer, Takeda, Tillots and Pharma. Fabienne Coury: received speaker/consulting fees from Abbvie, Amgen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, and grant/research support from Abbvie, Biogen, Celgene, Chugai, Novartis, Pfizer and UCB. Ben Braithwaite: no conflicts of interest to disclose. Salima Hateb: is an employee of and may hold stock in Biogen. Janet Addison: is an employee of and may hold stock in Biogen. Availability of data and material: The datasets generated and analysed during the current study are not publicly available as data for this study contain potentially identifying information. Ethics approval: All necessary ethical considerations and measures were taken to ensure the protection of all participants: patients were eligible for the study only if they were able to understand and sign a consent form. This study is listed on clinicaltrials.gov under the identifier NCT03662919 and was approved by the appropriate bodies in terms of quality of methodology, data security and scientific merit. The final amendment to the protocol for this study was approved by an independent ethics committee (Comité de Protection des Personnes, CPP) in France on 25 April 2019, in accordance with French regulations (CPP SUD-EST II; study ref. 2018-06; internal ref. 19.03.29.73319). Furthermore, this study conformed to all regulations concerning the use of personal data. All procedures were carried out in accordance with the ethical rules and the principles of the Declaration of Helsinki and its later amendments. Consent to participate: Informed consent was obtained from all individual participants included in the study in the form of a non-opposition form signed and archived by the physician in accordance with French regulations. Code availability: The code used to perform data management and run the analyses uses proprietary modules owned by eXYSTAT. Thus, the code cannot be made publicly available. Author contributions: Bruno Fautrel: as the coordinating investigator for rheumatology, made substantial contributions to the conception and design of the work, the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Yoram Bouhnik: as the coordinating investigator for gastroenterology, made substantial contributions to the conception and design of the work, the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Carine Salliot: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Mathurin Fumery: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Chirstophe Bernardeau: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Mathurin Flamant: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Fabienne Coury: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Ben Braithwaite: as the lead writer and biostatistics coordinator for this work, made substantial contributions to the design of the work, acquisition, analysis and interpretation of data for the work and produced all draft versions of the manuscript. Salima Hateb: as a study coordinator for the sponsor, made substantial contributions to the conception and design of the work, the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Janet Addison: as the sponsor’s lead scientist for this work, made substantial contributions to the conception and design of the work, the analysis and interpretation of data for the work and critically reviewed, commented upon and edited all draft versions of the manuscript. The first draft of the manuscript was written by Ben Braithwaite and all authors commented on previous versions of the manuscript. All authors read, provided input and approved the final manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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