Background Patients with RA experience a variety of signs and symptoms and report significant physical and psychological impairment. The RA Impact of Disease (RAID) scale is a disease-specific measure of the impact of RA on patients' lives. RAID was assessed in two Phase 3 randomized trials of sarilumab, a human monoclonal antibody directed against the IL-6 receptor-α (TARGET [NCT01709578]; MONARCH [NCT02332590]).
Objectives To evaluate patient-perceived impact of sarilumab on RA using the RAID scale vs either placebo + conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or adalimumab.
Methods TARGET assessed sarilumab 150mg and 200mg added to csDMARDs vs placebo in patients with RA intolerant of or not responding to anti-TNF therapy. MONARCH assessed sarilumab 200mg monotherapy vs adalimumab 40mg monotherapy in patients with RA either intolerant of, inadequate responders to, or considered inappropriate candidates for continued treatment with methotrexate. Treatments were administered subcutaneously every 2 weeks. RAID has 7 single-item domains, each rated by patients on an 11-point numeric rating scale from 0 (absence) to 10 (extreme). A total score from 0 to 10 (with lower scores indicative of less impact of disease) is calculated by weighting responses for each item based on patient assessment of the relative importance of the item. RAID was assessed at baseline (BL), Weeks 12 and 24. Least square mean (LSM) changes from BL in total score (Weeks 12 and 24) and domains (Week 24 only) were analysed with a mixed model for repeated measures, including treatment, region, visit, and treatment-by-visit interaction (and prior csDMARD therapy in TARGET) as fixed effects and BL as a covariate. RAID was tested outside of trial hierarchy and statistical significance is not claimed; nominal p-values are provided. Post-hoc categorical change analyses were conducted to identify “responders” in the total score (improvements ≥ minimum clinically important difference from BL to Week 24 [absolute change of 3 or relative change of 50% in total score]). Patients discontinuing therapy/requiring rescue medication prior to endpoint were classified as non-responders.
Results Sarilumab was superior (nominal p<0.05) to placebo (TARGET) and adalimumab (MONARCH) at Weeks 12 and 24 for RAID total score (Table). There was a greater proportion of responders in both sarilumab dose groups vs placebo at both time points (TARGET) and in sarilumab 200mg vs adalimumab at Week 24 (MONARCH). The effect of sarilumab was consistent across all 7 individual RAID domains (nominal p<0.05) at Week 24, except for sleep difficulties vs placebo in TARGET. Effects of placebo were highest on pain and effects of sarilumab were lowest on emotional well-being (TARGET) and coping (MONARCH).
Conclusions Assessed using RAID, sarilumab either with csDMARDs or as monotherapy reduced the impact of RA on patients' lives to a greater extent than placebo+csDMARDs or adalimumab monotherapy, with benefits shown on total RAID and all 7 individual domain scores.
Acknowledgements This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest L. Gossec Consultant for: Abbvie, Celgene, Janssen, Lilly, Novartis, MSD, Roche, and UCB, 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, C. Proudfoot Shareholder of: Sanofi, Employee of: Sanofi, C. Chen Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, S. Guillonneau Shareholder of: Sanofi, Employee of: Sanofi, T. Kimura Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, M. Reaney Shareholder of: Sanofi, Employee of: Sanofi