Efficacy and safety of sarilumab in combination with methotrexate in patients with active rheumatoid arthritis and inadequate effect of methotrexate monotherapy (results of phase III MOBILITY study)

Objective: to study the efficacy and safety of rheumatoid arthritis (RA) treatment with monoclonal antibodies to interleukin 6 receptors (IL6R) – sarilumab (SAR) in combination with methotrexate (MT). Subjects and methods. The study included adult patients with moderate or severe RA and inadequate effect of MT monotherapy. Patients were randomized in a 1:1:1 ratio to subgroups receiving SAR (at doses of 150 or 200 mg) or placebo (PL) every 2 weeks in combination with a weekly intake of MT for 52 weeks. The primary endpoints of the study included the achievement of ACR20 after 24 weeks, the change of HAQ-DI after 16 weeks and assessment of radiological progression of joint destruction (modified total Sharp score mTSS) after 52 weeks. Results and discussion. In general, the initial characteristics of patients were similar in all groups. A statistically significant improvement of all three primary endpoints was found in the groups of patients treated with SAR 150 and 200 mg compared to the group of PL. ACR20 response after 24 weeks was achieved in 53.6% (p<0.0005), 65.9 and 19.6% of patients respectively (p<0.0001), the average change in HAQ-DI after 16 weeks was 20.53; 20.55 and 20.29 respectively (p<0.0001); the average change in mTSS after 52 weeks was 0.49; 0.11 and 2.30, respectively (p<0.0001). Conclusion. Both doses of SAR (150 and 200 mg every 2 weeks) in combination with MT demonstrated sustained clinical efficacy in patients with RA, which was confirmed by a significant improvement in symptomatic, functional and radiographic outcomes. SAR therapy was generally well tolerated. The adverse events observed in this study were consistent with the effects of the IL6 blockade.