Objectives To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.
Methods This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured.
Results 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was −9.41% to 4.98%, which is completely contained within the predefined equivalence margin of −15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%).
Conclusions SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN.
Trial registration numbers NCT01895309, EudraCT 2012-005026-30.
- Rheumatoid Arthritis
- DMARDs (biologic)
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- Data supplement 1 - Online supplement
Handling editor Tore K Kvien
Correction notice This article has been corrected since it was published Online First. Several minor textual changes have been made and the author affiliations altered.
Contributors PE, JG and SYC were involved in the conception or design of the work, or the acquisition, analysis or interpretation of data, drafting the work or revising it critically for important intellectual content, final approval of the version published, and agreed 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. JV, AS, PL, WP, AB, VT, VZ, BS, RM and AB were involved in acquisition of data, drafting the work or revising it critically for important intellectual content, and final approval of the version published.
Funding This study was funded by Samsung Bioepis Co., Ltd.
Competing interests All authors received funding for clinical research from Samsung Bioepis: PE received consulting fees; JV, AS, PL, WP, AB, VT, VMZ, BS, RM, and AABR received research grants; SYC and JG are full-time employee of Samsung Bioepis. In addition, PE reports receiving grant/research support from AbbVie, Pfizer and consultancy fee from AbbVie, BMS, Pfizer, USB, MSD, Roche, Novartis, Takeda, Lilly; JV served on speakers bureau for USB, Pfizer, AbbVie, MSD; PL reports receiving grant/research support from Roche, MSD, Janssen, Novo-Nordisk, UCB, Pfizer, Novartis, GSK, BM, served as paid instructor for Novo-Nordisk, and served on speakers bureau for MSD, UCB, Roche, Amgen; AB reports receiving grant/research support from AbbVie.
Patient consent Obtained.
Ethics approval This study was conducted in compliance with the Declaration of Helsinki and Good Clinical Practice Guidelines established by the International Conference Harmonisation. The protocol was reviewed and approved by the institutional review board or the independent ethics committee of each investigational centre.
Provenance and peer review Not commissioned; externally peer reviewed.
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