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Extended report
A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy
  1. Paul Emery1,2,
  2. Jiří Vencovský3,
  3. Anna Sylwestrzak4,
  4. Piotr Leszczyński5,
  5. Wieslawa Porawska6,
  6. Asta Baranauskaite7,
  7. Vira Tseluyko8,
  8. Vyacheslav M Zhdan9,
  9. Barbara Stasiuk10,
  10. Roma Milasiene11,
  11. Aaron Alejandro Barrera Rodriguez12,
  12. Soo Yeon Cheong13,
  13. Jeehoon Ghil13
  1. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
  2. 2NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3Institute of Rheumatology, Prague, Czech Republic
  4. 4NZOZ Medica Pro Familia Sp. z o.o., Warsaw, Poland
  5. 5Poznan University of Medical Sciences, Poznan, Poland
  6. 6Poznanski Osrodek Medyczny NOVAMED, Pultusk, Poland
  7. 7Lithuanian University of Health Sciences, Kaunas, Lithuania
  8. 8Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine
  9. 9M.V.Sklifosovskyi Poltava Regional Clinical Hospital, Poltava, Ukraine
  10. 10Medicome Sp. z o.o., Oswiecim, Poland
  11. 11Klaipeda University Hospital, Klaipeda, Lithuania
  12. 12Unidad de Atención Medica e Investigación en Salud (UNAMIS), Yucatán, México
  13. 13Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
  1. Correspondence to Professor Paul Emery, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK; p.emery{at}leeds.ac.uk

Abstract

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.

  • Anti-TNF
  • Rheumatoid Arthritis
  • DMARDs (biologic)

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • 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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