RESUMO
OBJECTIVES: To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA). METHODS: In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100â mg q2w, 150â mg q2w, 100â mg qw, 200â mg q2w, 150â mg qw for 12â weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed. RESULTS: The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150â mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150â mg q2w (67%; unadjusted (nominal) p=0.0363) and 200â mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150â mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors. CONCLUSIONS: Sarilumab improved signs and symptoms of RA over 12â weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150â mg and sarilumab 200â mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.