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Original research
Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis
  1. Josef S Smolen1,
  2. Jung-Yoon Choe2,
  3. Michael E Weinblatt3,
  4. Paul Emery4,
  5. Edward Keystone5,
  6. Mark C Genovese6,
  7. Gihyun Myung7,
  8. Evelyn Hong7,
  9. Inyoung Baek7 and
  10. Jeehoon Ghil7
  1. 1Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria
  2. 2Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea
  3. 3Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  4. 4University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK
  5. 5Divison of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  6. 6Division of Immunology and Rheumatology, Stanford University Medical Center, Stanford, California, USA
  7. 7Samsung Bioepis Co Ltd, Incheon, Republic of Korea
  1. Correspondence to Dr Josef S Smolen; josef.smolen.ard{at}


Objective To evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status.

Methods Patients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models.

Results 1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI.

Conclusion A pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity.

Trial registration numbers NCT01895309, NCT01936181 and NCT02167139

  • anti-TNF
  • rheumatoid arthritis
  • DMARDs (biologic)
  • arthritis

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  • Funding This work was supported by Samsung Bioepis Co, Ltd.

  • Competing interests JSS has received personal remuneration from AbbVie, Amgen, Astra-Zeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Novo-Nordisk, Pfizer, Roche, Samsung, Sanofi and UCB and research funding from AbbVie, Janssen, Lilly, Novartis-Sandoz, Pfizer and Roche. MEW has received research funding from Bristol-Myers Squibb, Crescendo Bioscience and Sanofi/Regeneron; has served as a consultant and/or advisory board member for AbbVie, Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Corrona, GSK, Gilead, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung Bioepis and Set Point; and has financial interests/stock ownership in Lycera, Canfite, Scipher and Vorso. PE has been a clinical trials investigator and advisor to Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly and has received consulting fees from Bristol-Myers Squibb, AbbVie, Gilead, Pfizer, MSD, Novartis, Roche and UCB; his employer has received research grants from AbbVie, Bristol-Myers Squibb, Pfizer, MSD and Roche. EK has received research funding from AbbVie, Amgen, Lilly, Gilead, Pfizer, PuraPharm, Sanofi and Merck; has served as a consultant and/or advisory board member for AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Crescendo Bioscience, Roche, Genentech, Gilead, Janssen, Lilly, Merck, Pfizer, Sandoz, Sanofi and Samsung Bioepis; and has received speaker honoraria for Amgen, AbbVie, Bristol-Myers Squibb, Roche, Janssen, Merck, Pfizer, Sanofi and UCB. MCG has received research funding from AbbVie; has received consulting fees from Samsung Bioepis, Merck, Abbvie, Amgen and FKB. GM, EH, IB and JG are employees of Samsung Bioepis.

  • Patient consent for publication Not required.

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

  • Data availability statement Upon request, and subject to certain criteria, conditions and exceptions, Samsung Bioepis will provide access to individual deidentified participant data. The deidentified participant data will be made available to researchers whose proposals meet the research criteria and other conditions and for which an exception does not apply. To gain access, data requestors who intend to obtain data should send the proposals to the corresponding author. To gain access, data requestors must enter into a data access agreement with Samsung Bioepis.

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