Background/Purpose: Sarilumab is the first fully human monoclonal antibody directed against IL-6Rα. Part A of the MOBILITY phase 2/3 seamless study evaluated the efficacy and safety of 5 dose regimens of subcutaneous sarilumab on top of methotrexate (MTX) versus placebo plus MTX, for the treatment of rheumatoid arthritis (RA).
Methods: MOBILITY Part A was a phase 2, 12-week, multi-national, double-blind trial that included adults with active, moderate-to-severe RA who had an inadequate response to treatment with MTX. Patients on background MTX were randomized to 6 groups: sarilumab 100 mg every other week (q2w), 150 mg q2w, 100 mg weekly (qw), 200 mg q2w, 150 mg qw, or placebo. The primary endpoint was the proportion of patients achieving a ³20% improvement in the American College of Rheumatology criteria ACR20 at Week 12. Safety and tolerability were also assessed.
Results: 306 patients were randomized. Baseline demographic and disease characteristics were similar across groups: mean age 52 years; 79% female; and mean disease duration 8 years with mean tender joint count 27, mean swollen joint count 17, mean CRP 2.8 mg/dL, and mean health assessment question-disability 1.6. ACR20 response at Week 12 was numerically higher than placebo in 4 sarilumab dose groups, and significantly greater in the 150 mg qw sarilumab arm (72.0%) compared to placebo (46.2%) (P=0.02).
The percentage of patients with ³1 treatment emergent adverse event (AE) ranged from 43% to 72% for the sarilumab groups versus 47% for placebo. The most common treatment emergent AEs reported by patients in the active treatment arms were infections (non-serious) 12-26%, neutropenia 0-20%, and ALT increase 0-6%. One patient receiving sarilumab (150 q2w arm) experienced an opportunistic infection (herpes zoster facialis) and recovered. Eight patients (3 receiving sarilumab 100 mg q2w, 3 receiving 100 mg qw, and 2 receiving placebo) experienced at least 1 treatment emergent serious AE. One death (stroke/acute respiratory distress syndrome) occurred in a patient treated with sarilumab 100 mg q2w. Increases in total cholesterol, LDL and HDL were seen with sarilumab.
Conclusions: In this phase 2 study, sarilumab in combination with methotrexate demonstrated efficacy in patients with active, moderate-to-severe rheumatoid arthritis. The types and incidence of adverse events were consistent with those previously reported with IL-6 inhibition. Part B, the phase 3 portion of the MOBILITY seamless study, will assess long-term efficacy of sarilumab in rheumatoid arthritis.
Disclosure: M. C. Genovese, Sanofi-Aventis Pharmaceutical, 2, Sanofi-Aventis Pharmaceutical, 5 ; A. J. Kivitz, None; J. A. Simon Campos, None; M. Rell-Bakalarska, None; R. M. Fleischmann, Sanofi-Aventis Pharmaceutical, 2, Sanofi-Aventis Pharmaceutical, 5, Regeneron, 2, Regeneron, 5 ; M. Jasson, Sanofi-Aventis Pharmaceutical, 1, Sanofi-Aventis Pharmaceutical, 3 ; A. R. Radin, Regeneron, 1, Regeneron, 3 ; X. Huang, Sanofi-Aventis Pharmaceutical, 3 ; T. W. J. Huizinga, Merck Pharmaceuticals, 5, U.C. B., 5, Bristol-Myers Squibb, 5, Biotest AG, 5, Pfizer Inc, 5, Novartis Pharmaceutical Corporation, 5, Roche Pharmaceuticals, 5, Sanofi-Aventis Pharmaceutical, 5, Abbott Laboratories, 5, Crescendo Bioscience, 5, Nycomed, 5, Axis-Shield, 5, Roche Pharmaceuticals, 9, Abbott Laboratories, 9 .