Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis

Abstract

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.

Keywords: DMARDs (biologic); anti-TNF; arthritis; rheumatoid arthritis.

Conflict of interest statement

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.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

One-year radiographic progression in mean change in mTSS based on DAS28 (per erythrocyte sedimentation rate), SDAI scores and CDAI scores at week 24/30. CDAI, Clinical Disease Activity Index; DAS28, disease activity score based on 28-joint count; HDA, high disease activity; LDA, low disease activity; MDA, moderate disease activity; mTSS, modified Total Sharp Score; SDAI, Simplified Disease Activity Index. *Estimated difference in reference to remission with p

Figure 2

Proportion of radiographic progressors and non-progressors based on DAS28 (per erythrocyte sedimentation rate), SDAI scores and CDAI scores at week 24/30. CDAI, Clinical Disease Activity Index; DAS28, disease activity score based on 28-joint count; HDA, high disease activity; LDA, low disease activity; MDA, moderate disease activity; SDAI, Simplified Disease Activity Index.

Figure 3

ORs of radiographic non-progressors in reference to remission by disease activity score based on 28-joint count (per erythrocyte sedimentation rate) at (A) week 24/30 and (B) week 12/14 in all treatments combined group. DAS, disease activity score; HDA, high disease activity; LDA, low disease activity; MDA, moderate disease activity.

Figure 4

Cumulative probability plot of 1-year radiographic progression based on (A) DAS using 28-joint count (per erythrocyte sedimentation rate), (B) SDAI scores and (C) CDAI scores. CDAI, Clinical Disease Activity Index; DAS, disease activity score; HDA, high disease activity; LDA, low disease activity; MDA, moderate disease activity; mTSS, modified Total Sharp Score; SDAI, Simplified Disease Activity Index.