Background The phase 3 MONARCH superiority study (NCT02332590) compared efficacy and safety of sarilumab (a human anti-IL-6Rα monoclonal antibody [mAb]) 200 mg administered subcutaneously every 2 weeks (q2w), with adalimumab (an anti-TNF-α mAb) 40 mg administered q2w, in patients with active rheumatoid arthritis (RA) who were either intolerant of, or inadequate responders to methotrexate treatment. Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy in reduction of disease activity and improvements in physical function and signs and symptoms of RA, with safety and tolerability consistent with IL-6R or TNF blockade.
Objectives To compare patient-reported outcomes (PROs) with sarilumab vs adalimumab from MONARCH.
Methods PROs assessed at baseline, weeks 12 and 24 included ACR components (Patient Global Assessment of Disease Activity [PtGA], Pain visual analog scale [VAS], Health Assessment Questionnaire Disability Index [HAQ-DI]), Medical Outcomes Study Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Morning Stiffness VAS, RA Impact of Disease (RAID) and RA-specific Work Productivity Survey (WPS-RA). Least-squares mean (LSM) between-group differences were determined by mixed-model for repeated measures with treatment, visit, treatment-by-visit interaction and region as fixed effects, and the corresponding baseline PRO scores as continuous covariates. A P-value <0.05 was considered statistically significant for PROs in a predefined hierarchy (ACR components, SF-36 physical component summary [PCS], FACIT-F and SF-36 mental component summary [MCS] scores). For PROs not in the hierarchy, significance is not claimed. Changes from baseline were compared with published values for minimum clinically important differences (MCIDs).
Results Baseline demographics, disease characteristics and PROs were generally balanced between treatment groups (n=184 sarilumab; n=185 adalimumab). Improvements from baseline to week 24 were greater with sarilumab vs adalimumab across PtGA, Pain VAS, HAQ-DI, SF-36 PCS, Morning Stiffness VAS, RAID and WPS-RA global scores (all P<0.05, statistical significance is claimed only for PROs in the hierarchy; see table). Between-group differences in FACIT-F and SF-36 MCS scores were not significant. Improvements ≥MCID were reported by a greater percentage of patients with sarilumab than adalimumab for HAQ-DI (≥0.22 units), RAID (≥3 units), SF-36 PCS (≥2.5), and Morning Stiffness VAS (≥10) (all nominal P<0.05).
Conclusions Sarilumab monotherapy compared with adalimumab monotherapy resulted in greater and clinically meaningful improvements in many PROs, including patient-reported disease activity, pain, physical function, morning stiffness, productivity, health related quality of life and health status.
Acknowledgements This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest V. Strand Consultant for: AbbVie, Amgen, AstraZeneca, Biogen, BMS, Celltrion, CORRONA, Crescendo, Genentech/Roche, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz, Sanofi, and UCB, L. Gossec Grant/research support from: Member of institution that received research funding for the current study, C. Proudfoot Shareholder of: Sanofi, Employee of: Sanofi, C. Chen Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., M. Reaney Shareholder of: Sanofi, Employee of: Sanofi, S. Guillonneau Shareholder of: Sanofi, Employee of: Sanofi, T. Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Pfizer Inc. and Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, G. R. Burmester Grant/research support from: Member of institution that received research funding for the current study