Background Sarilumab, a fully human monoclonal antibody directed against IL-6R, in combination with methotrexate (MTX) showed efficacy in patients with active, moderate-to-severe rheumatoid arthritis (RA) with an inadequate response to MTX in the phase 3 part of the MOBILITY (NCT01061736) study.1 Although biologic DMARDs are increasingly used to manage moderately active RA, responses to these treatment are less well studied in this patient population.
Objectives To further explore in a post hoc analysis the efficacy and safety of sarilumab in patients with moderate and severe disease in the MOBILITY study.
Methods Adults with active, moderate-to-severe RA and inadequate response to MTX were randomized 1:1:1 to placebo (Pbo), sarilumab 150 mg q2w, or sarilumab 200 mg q2w plus background MTX for 52 wks. Primary endpoints were: 1) ACR20 response at Wk 24; 2) change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Wk 16 and; 3) change from baseline in van der Heijde modified total Sharp score (mTSS) at Wk 52. Secondary efficacy endpoints included major ACR50 and ACR70 responses, and reduction in Disease Activity Score 28-C-reactive protein (DAS28-CRP). In this post hoc analysis, data were analyzed by disease activity at baseline (DAS28-CRP: moderate, >3.2 but ≤5.1; severe, >5.1) in the intent-to-treat population.
Results MOBILITY enrolled 18% patients with moderate, 82% with severe disease activity Demographics were similar in moderate and severe groups; the severe RA group had higher baseline indices of disease activity (tender/swollen joint counts, CRP, HAQ-DI, DAS28-CRP). Similar ACR20, ACR50 and ACR70 responses were noted for moderate and severe groups receiving sarilumab (Table). Reductions in Clinical Disease Activity Index were numerically greater with sarilumab vs placebo at Wk 24; this effect was maintained at Wk 52 in moderate and severe RA. DAS28-CRP was also reduced with sarilumab vs placebo in moderate and severe RA groups. Further reductions were noted at Wk 52 in DAS28-CRP at Wk 24. Changes from baseline in mTSS were numerically less with sarilumab vs placebo in moderate and severe RA groups. Adverse events (AE) and serious AEs were more frequent in Pbo, and similar in sarilumab groups with moderate and severe disease (any AE: moderate, Pbo, 66.3%; 150 mg, 76.1%; 200 mg, 80.6%; severe, Pbo, 60.3%; 150 mg, 74.6%; 200 mg, 77.6%). The most common TEAEs included infections and injection site reactions. Lab abnormalities included decreases in neutrophils and increases in transaminases and lipids.
Conclusions In this study, numeric improvements in signs and symptoms of RA and less progression of joint damage were observed in sarilumab patients with severe and moderate RA. The incidence of AEs was generally similar in sarilumab treatment arms for patients with moderate and severe disease.
Genovese M et al. Abstr. No. EULAR14-SCIE-3001 presented at EULAR 2014, Paris, France
Acknowledgements The study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Editorial support was provided by Tara Miller of Envision Scientific Solutions and was funded by Sanofi and Regeneron Pharmaceuticals Inc.
Disclosure of Interest M. Genovese: None declared, D. Nguyen Shareholder of: AbbVie, Employee of: Sanofi, H. van Hoogstraten Employee of: Regeneron, J. van Adelsburg Shareholder of: Regeneron, Employee of: Regeneron, R. Wu: None declared, T. Huizinga Consultant for: Merck, UCB, BMS, Biotest AG, Pfizer, Novartis, Roche, Sanofi, Abbott, Crescendo Bioscience, Nycomed, Boeringher Ingelheim, Takeda, Zydus, and Eli Lilly