Background/Purpose: Sarilumab is a human mAb that blocks IL-6 from binding to both membrane-bound and soluble IL-6Rα. Efficacy and safety of sarilumab + non-biologic DMARDs have been demonstrated.^1,2 However, 30% of patients with RA use biologics as monotherapy because of intolerance or contraindications to combination therapy.³ In this phase 3 trial, safety and efficacy of sarilumab monotherapy were compared with adalimumab monotherapy in adult patients with active RA (NCT02332590).

Methods: Adults (N=369) intolerant of, inappropriate for, or inadequate responders to MTX received subcutaneous sarilumab (200 mg every 2 weeks [q2w]) or adalimumab (40 mg q2w) monotherapy for 24 weeks in this double-blind, double-dummy superiority study. Starting at week 16, patients with inadequate response could increase to weekly adalimumab (or matching placebo). The primary endpoint, change from baseline in DAS28-ESR at week 24, was assessed using a mixed model for repeated measures analysis. Secondary endpoints, including clinical disease activity index (CDAI), were also assessed (Table).

Results: Baseline demographics and disease characteristics were generally comparable between treatment groups. At week 24, significantly greater decrease in DAS28-ESR scores, greater incidence of DAS28-ESR remission and ACR20/50/70 responses, and improvement in HAQ–Disability Index were observed with sarilumab vs adalimumab (Table); results included patients switching to weekly adalimumab. Patients in the sarilumab group were twice as likely to achieve CDAI remission at week 24 vs adalimumab (nominal P<0.05). Incidences of adverse events (AEs) (64%) and serious AEs (sarilumab, 5%; adalimumab, 7%) were similar between groups. Neutropenia and injection site reactions were more common with sarilumab; headache and worsening of RA were more common with adalimumab. Incidences of infections (sarilumab, 29%; adalimumab, 28%) and serious infections (1%) were similar between groups. Neutropenia was not associated with an increased incidence of infections. Most injection site reactions were mild; only 2 cases led to treatment discontinuation in the sarilumab group. There was 1 death in the sarilumab group, 35 days after initiating treatment, due to acute cardiac failure.

Conclusion: Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy in reduction of disease activity and improvement in signs and symptoms and physical function in patients with active RA who were inappropriate candidates for continued treatment with MTX due to intolerance or inadequate response. The overall incidences of AEs and serious AEs were similar between groups, as was the rate of infections and serious infections. References: 1. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437. 2. Fleischmann et al. Presented at: ACR; November 7-11, 2015; San Francisco, CA. 3. Emery et al. Ann Rheum Dis. 2013;72:1897-1904.