Background Clinical remission is an important treatment goal in rheumatoid arthritis (RA) and is associated with improved physical function and quality of life.1,2 In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously every 2 weeks + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) demonstrated efficacy in adults with active, moderate-to-severe RA and inadequate response to tumor necrosis factor (TNF) inhibitors.3 Infections, neutropenia, injection site reactions, and increased transaminases were among the most common treatment-emergent adverse events.3
Objectives This analysis assessed the proportions of patients achieving clinical remission measured by 4 different disease activity measures in a difficult-to-treat patient population with active RA and inadequate response or intolerance to ≥1 prior TNF inhibitor(s).
Methods Four definitions of remission were used: 28-joint disease activity score by C-reactive protein (DAS28-CRP) <2.6, clinical disease activity index (CDAI) ≤2.8, simplified disease activity index (SDAI) ≤3.3, and Boolean-based ACR/EULAR remission (tender and swollen joint counts [28 joints] ≤1, CRP ≤10 mg/L, and patient global visual analog scale ≤10 mm/100 mm). Differences in incidence of these benchmarks between the active treatment groups and placebo were assessed using 2-sided Cochran-Mantel-Haenszel tests stratified by geographic region and number of prior TNF inhibitors. Patients who started rescue medication or discontinued the study were considered not to be in remission (nonresponder imputation).
Results Baseline demographic and disease characteristics were balanced among the 3 treatment groups. At week (wk) 12 and wk 24, the proportion of patients achieving DAS28-CRP <2.6, CDAI, SDAI, and Boolean-based remission was higher in the sarilumab-treated groups than in the placebo group (Table). At wk 24, a significantly greater proportion of sarilumab patients achieved DAS28-CRP <2.6 compared with placebo. In comparison with placebo patients, a greater proportion of sarilumab patients who achieved DAS28-CRP <2.6 or Boolean-based remission also had clinically meaningful improvements in Health Assessment Questionnaire–Disability Index (HAQ-DI) and Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) at wk 24 (Table).
Conclusions Sarilumab induced remission (using a broad range of definitions) as early as 12 weeks after initiation of therapy in patients with an inadequate response to TNF inhibitors. Patients with remission generally had improvements in physical function and fatigue as well.
Smolen et al. Ann Rheum Dis. 2014;73:492–509.
Radner et al. Arthritis Res Ther. 2014;16:R56.
Fleischmann et al. Presented at: ACR; November 7–11, 2015; San Francisco, CA.
Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest G. Burmester Grant/research support from: AbbVie, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, Pfizer, Merck, MedImmune, UCB, and Roche, Speakers bureau: AbbVie, BMS, Pfizer, Merck, UCB, and Roche, P. Hrycaj: None declared, C. Pacheco-Tena Consultant for: BMS, Janssen, Pfizer, Roche, and UCB, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, D. Bauer Shareholder of: Sanofi, Employee of: Sanofi, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Parrino Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Kivitz Shareholder of: Sanofi and Regeneron Pharmaceuticals, Inc., Consultant for: Sanofi, Pfizer, Roche, and UCB