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Extended report
A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy
  1. Jung-Yoon Choe1,
  2. Nenad Prodanovic2,
  3. Jaroslaw Niebrzydowski3,
  4. Ivan Staykov4,
  5. Eva Dokoupilova5,
  6. Asta Baranauskaite6,
  7. Roman Yatsyshyn7,
  8. Mevludin Mekic8,
  9. Wieskawa Porawska9,
  10. Hana Ciferska10,
  11. Krystyna Jedrychowicz-Rosiak11,
  12. Agnieszka Zielinska12,
  13. Jasmine Choi13,
  14. Young Hee Rho13,
  15. Josef S Smolen14
  1. 1Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
  2. 2Clinical Center Banja Luka, Banja Luka, Bosnia and Herzegovina
  3. 3Medica Pro Familia, Gdynia, Poland
  4. 4MHAT “Dr. Ivan Seliminski”, AD, Sliven, Bulgaria
  5. 5MEDICAL PLUS s.r.o, Uherske Hradiste, Czech Republic
  6. 6Lithuanian University of Health Sciences, Kaunas, Lithuania
  7. 7Internal Medicine #1 Department, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine
  8. 8University Clinic Centre Sarajevo, Sarajevo, Bosnia and Herzegovina
  9. 9Poznanski Osrodek Medyczny NOVAMED, Poznan, Poland
  10. 10Institute of Rheumatology and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
  11. 11MCBK S.C., Grodzisk Mazowiecki, Poland
  12. 12Medica Pro Familia Sp. z o.o. Spolka Komandytowo-Akcyjna, Warszawa, Poland
  13. 13Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
  14. 14Medical University of Vienna, Vienna, Austria
  1. Correspondence to Professor Josef S Smolen, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; josef.smolen{at}wienkav.at

Abstract

Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.

Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence.

Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF.

Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF.

Trial registration number NCT01936181.

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

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Footnotes

  • Handling editor Tore K Kvien

  • A portion of the manuscript was presented as an abstract (SAT0152) at Rome in EULAR 2015.

  • Correction notice This article has been corrected since it was published Online First. Minor corrections have been made to the author affiliations, funding section and table 2.

  • Contributors JSS, JC and YHR contributed to study conception and design, acquisition of data, analysis and interpretation of data, drafting the manuscript and revising it critically for important intellectual content, and final approval of the version to be published. J-YC contributed to acquisition of data, analysis and interpretation of data, drafting the manuscript and revising it critically for important intellectual content, and final approval of the version to be published. NP, JN, IS, ED, AB, RY, MM, WP, HC, KJ-R and AZ contributed to acquisition of data, drafting of the manuscript and revising it critically for important intellectual content, and final approval of the version to be published. YHR wrote the paper on behalf of the sponsor. There were no professional writers or companies hired for this purpose. All coauthors contributed significantly to the writing of the manuscript.

  • Funding This study was funded by Samsung Bioepis Co., Ltd.

  • Competing interests J-YC reports receiving grant/research support and consultant fees from Samsung Bioepis. JSS reports receiving grant/research support from AbbVie, Jassen, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Astro-Pharma, Celgene, GSK, Jassen, Lilly, Medimmune, MSD, Norvartis-Sandoz, Novo Nordisk, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB. AB reports receiving grant/research support from AbbVie and Samsung Bioepis. NP, JN, IS, ED, RY, MM, WP, HC, KJ-R and AZ report receiving grant/research support from Samsung Bioepis. JC and YHR are employees of Samsung Bioepis.

  • Ethics approval Each national regulatory agency and central or local ethical committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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