SAT0180 Onset of Action of Sarilumab in Patients with Rheumatoid Arthritis in 2 Phase 3 Studies
Authors: R. Fleischmann, E.K. Mangan, J. van Adelsberg, J. Fay, H. van Hoogstraten, D. Bauer, D. Thompson, A. Kivitz, G.R. Burmester
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The investigational human anti–interleukin 6 receptor monoclonal antibody sarilumab plus methotrexate (MTX) has demonstrated efficacy in patients with rheumatoid arthritis (RA) and inadequate response to MTX (MOBILITY; NCT01061736),<sup>1</sup> while sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) demonstrated efficacy in patients with RA and inadequate response or intolerance to tumor necrosis factor (TNF) inhibitors (TARGET; NCT01709578).<sup>2</sup> Among the most common treatment-emergent adverse events in both studies were infections, neutropenia, injection site reactions, and increased transaminases. <h3>Objectives</h3> This analysis of MOBILITY and TARGET study data assessed the time to onset of clinical efficacy of sarilumab and the durability of response over 24 weeks. <h3>Methods</h3> Adults with active, moderate-to-severe RA were randomized to 1 of 3 groups receiving subcutaneous sarilumab 150 or 200 mg or placebo every 2 weeks (q2w) plus background MTX (MOBILITY) or csDMARDs (TARGET). Clinical efficacy was evaluated in these patients at weeks 2, 4, 8, 12, and 24 in a post hoc analysis. ACR20/50/70 response rates were analyzed using the 2-sided Cochran-Mantel-Haenszel test stratified by prior biologic use and region (MOBILITY) or by region and number of prior TNF inhibitors (TARGET); nonresponder imputation was applied for patients who started rescue medication or discontinued the study. Changes from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI), 28-joint disease activity score by C-reactive protein (DAS28-CRP), and clinical disease activity index (CDAI) were analyzed with a mixed model for repeated measures; no data were imputed. <h3>Results</h3> Baseline demographic and disease characteristics were similar between treatment groups in both studies.<sup>1,2</sup> Improvements in ACR20 responses were observed as early as week 2 in both studies, with nominal <i>P</i>&lt;0.05 observed at week 8 for all sarilumab-treated groups in both studies. Similar trends were observed for ACR50 and ACR70 responses. Greater reductions in DAS28-CRP mean change from baseline vs placebo were observed with both doses of sarilumab by week 2 in both studies (nominal <i>P</i>&lt;0.05). Similarly, numerical improvements in HAQ-DI and CDAI were observed with both doses of sarilumab vs placebo by week 4 in both studies (nominal <i>P</i>&lt;0.05; Table). Improvements in all efficacy parameters were sustained through the end of each study (ie, week 52 for MOBILITY and week 24 for TARGET). The most common treatment-emergent adverse events at week 12 were infection and neutropenia, consistent with the safety profile previously reported for the entire study periods. <h3>Conclusions</h3> Sarilumab rapidly improved signs and symptoms of RA in patients with inadequate response to MTX (MOBILITY) or TNF inhibitors (TARGET), and improvements were sustained through the end of treatment. <h3>References</h3> Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437 Fleischmann et al. Presented at: ACR; Nov. 7–11, 2015; San Francisco, CA <h3>Acknowledgement</h3> 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. <h3>Disclosure of Interest</h3> R. Fleischmann Grant/research support from: AbbVie, Amgen, Ardea Biosciences, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Eli Lilly, Pfizer, Roche, Sanofi, and UCB, Consultant for: AbbVie, Akros Pharma, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche, and UCB, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, D. Bauer Shareholder of: Sanofi, Employee of: Sanofi, D. Thompson 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, G. Burmester: None declared