Background Sarilumab, a human mAb blocking the IL-6Rα, was evaluated in 3 pivotal clinical trials.

Objectives To assess efficacy and safety of sarilumab 200 mg q2w + csDMARDs or as monotherapy (MONARCH) in adults with active RA and inadequate response or intolerance to MTX (MOBILITY/MONARCH) or TNFi (TARGET).

Methods MOBILITY (NCT01061736) was a 52-wk study; TARGET (NCT01709578) and MONARCH (NCT02332590) were 24-wk studies. Patients were randomized to placebo (Pbo) or SC sarilumab 150 or 200 mg q2w + MTX (MOBILITY) or csDMARDs (TARGET). MONARCH patients were randomized to SC monotherapy with adalimumab 40 mg q2w or sarilumab 200 mg q2w. Efficacy endpoints assessed in all 3 studies will be presented.

Results Within studies, baseline demographic and disease characteristics were similar among treatment groups. Sarilumab 200 mg q2w improved ACR responses, HAQ-DI, DAS28-CRP, and CDAI (Table). Treatment response with sarilumab + csDMARDs was similar in MTX-IR and TNF-IR patients and with sarilumab monotherapy. Incidence of TEAEs and SAEs with sarilumab was more frequent vs Pbo (MOBILITY, TARGET) and similar to adalimumab (MONARCH). The most common TEAEs included infections, neutropenia, and injection site reactions and occurred more often with sarilumab vs Pbo (MOBILITY, TARGET). In MONARCH, rates of infection were similar with sarilumab and adalimumab, although neutropenia was more frequent with sarilumab. Safety of sarilumab was generally comparable in monotherapy and combination studies; monotherapy was associated with fewer ALT elevations >3 × ULN compared with combination therapy: MONARCH, 3%; MOBILITY, 8%; TARGET, 4%.

Conclusions Sarilumab 200 mg q2w + csDMARDs significantly reduced disease activity and improved physical function to a similar extent regardless of population (MTX-IR or TNF-IR) and as monotherapy. Safety profile of sarilumab was generally comparable across all 3 trials, with monotherapy resulting in fewer ALT elevations.

Acknowledgements This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by MedThink SciCom and funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.

Disclosure of Interest M. Genovese Grant/research support from: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, Consultant for: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, R. Fleischmann Grant/research support from: AbbVie, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Pfizer, Roche, Sanofi, and UCB, Consultant for: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche, and UCB, H. van Hoogstraten Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, S. Jayawardena Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, G. Burmester Grant/research support from: AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche, and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and UCB