Efficacy and safety of sarilumab versus adalimumab in a phase 3, randomized, double-blind, monotherapy study in patients with active rheumatoid arthritis with intolerance or inadequate response to methotrexate

Aim: Sarilumab is a human mAb blocking the IL‐6Ralpha. Efficacy and safety of sarilumab + non‐biologic DMARDs have been demonstrated. In this phase 3 trial, efficacy and safety 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 q2w) or adalimumab (40 mg q2w) monotherapy for 24 weeks in this doubleblind, double‐dummy, superiority study. Starting at week 16, patients with inadequate response could increase to weekly adalimumab (or matching placebo). The primary endpoint was change from baseline in DAS28‐ESR at week 24. Results: Baseline demographics and disease characteristics were generally comparable between treatment groups. At week 24, significantly greater decrease in DAS28‐ESR (‐3.3 vs 2.2; P < 0.0001), greater incidence of DAS28‐ESR remission (26.6% vs 7.0%; P < 0.0001) and ACR20/50/70 responses (71.7%/45.7%/23.4% vs 58.4%/29.7%/11.9%; all P <= 0.0074), and improvement in HAQ‐DI (‐0.6 vs ‐0.4; P = 0.0037) were observed with sarilumab vs adalimumab; 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). The incidences of AEs and serious AEs were similar in both groups, including incidences of infections and serious infections. The most common AEs were neutropenia and injection site erythema (sarilumab) and headache and worsening of RA (adalimumab). Conclusions: Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy in reduction of disease activity and improvement in 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.