Background Efficacy, including improvements in patient-reported outcomes (PROs), was demonstrated in 2 phase 3 trials, MOBILITY1 (NCT01061736) and TARGET2 (NCT01709578), of sarilumab, an investigational human anti–interleukin 6 receptor monoclonal antibody. The most common treatment-emergent adverse events in both studies were infections, neutropenia, injection site reactions, and increased transaminases.
Objectives To evaluate the early onset of benefit of sarilumab treatment measured by PROs.
Methods In both studies, adults with moderate-to-severe, active rheumatoid arthritis (RA) were randomized to 1 of 3 groups receiving placebo, sarilumab 150 mg, or sarilumab 200 mg subcutaneously (SC) every 2 weeks (q2w) plus methotrexate (MTX; MOBILITY) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; TARGET). PROs assessed as early as week 2 included patient global assessment of disease activity (PtGA), pain assessed by visual analog scale (VAS), Health Assessment Questionnaire–Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), sleep by VAS (MOBILITY), and AM stiffness by VAS (TARGET). Changes from baseline were analyzed using mixed-model repeated measures with region, number of prior tumor necrosis factor inhibitors (TNFis) (TARGET) or prior biologic use (MOBILITY), visit, treatment, treatment-by-visit interaction, and baseline PRO scores as covariates.
Results Greater improvements were reported by patients treated with sarilumab 150 and 200 mg SC q2w vs placebo as early as week 2 in PtGA, pain VAS, HAQ-DI, FACIT-F, sleep VAS, and AM stiffness VAS (nominal P<0.05) (Figure) and sustained through week 24. Between-group differences were statistically significant for FACIT-F and sleep VAS at week 24 in MOBILITY and for HAQ-DI at week 12 (TARGET) and week 16 (MOBILITY).
Conclusions Sarilumab treatment rapidly improved a broad range of PROs in patients with RA with inadequate response to MTX (MOBILITY) or TNFis (TARGET); these improvements were observed as early week 2 and maintained through week 24. The results demonstrate the early benefit of sarilumab treatment based on patients' own assessments of their disease.
Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437.
Fleischmann et al. Arthritis Rheumatol. 2015;67(suppl 10).
Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest V. Strand Consultant for: AbbVie, Amgen, AstraZeneca, Biogen, BMS, Celgene, Celltrion, Consortium of Rheumatology Researchers of North America (CORRONA), Crescendo/Myriad Genetics, EMD Serono, Genentech/Roche, GSK, Janssen, Eli Lilly, Novartis, Pfizer Inc, Regeneron Pharmaceuticals, Inc, Sandoz, Sanofi, and UCB, C. Chen Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, P. Mahajan Shareholder of: Sanofi, Employee of: Sanofi, M. Kosinski Consultant for: Sanofi and Regeneron, E. Mangan Shareholder of: in Pfizer Inc and Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, N. Graham Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, E. Keystone Consultant for: has consulting agreements/advisory board membership with Abbott, AstraZeneca, Biotest, BMS, F. Hoffman-La Roche, Genentech, Janssen, Eli Lilly, Merck, Pfizer Inc, and UCB; and has speaker honoraria agreements with Abbott, Amgen, AstraZeneca, BMS Canada, F. Hoffman-La Roche, Janssen, Pfizer Inc, and UCB., J. Braun Grant/research support from: received honoraria for talks, advisory boards, paid consultancies, and grants for studies from AbbVie (Abbott), Amgen, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Hospira, Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer Inc (Wyeth), Roche, Sanofi-Aventis, and UCB, Consultant for: received honoraria for talks, advisory boards, paid consultancies, and grants for studies from AbbVie (Abbott), Amgen, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Hospira, Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer Inc (Wyeth), Roche, Sanofi-Aventis, and UCB
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