Sarilumab is a human monoclonal anti–interleukin (IL)-6 receptor alpha antibody that inhibits IL-6-mediated signaling effects. In the phase 3, 24-week MOBILITY and 52-week TARGET studies, subcutaneous sarilumab (150 mg or 200 mg every 2 weeks [q2w]) plus background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) demonstrated efficacy and safety in patients with active, moderate-to-severe rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX) or inadequate response to, or intolerance of, tumor necrosis factor (TNF) inhibitors. The objective of this post-hoc analysis was to assess the proportion of patients who achieved clinical remission or low disease activity (LDA) by week 24 (TARGET) and week 52 (MOBILITY).
In both trials, adults with active RA were randomized 1:1:1 to receive sarilumab 150 mg or 200 mg q2w or placebo + MTX (MOBILITY) or csDMARDs (TARGET). Clinical remission and LDA were assessed using Disease Activity Score 28–C-reactive protein (DAS28-CRP; <2.4 and ≤2.9), Clinical Disease Activity Index (CDAI; ≤2.8 and ≤10), and Simplified Disease Activity Index (SDAI; ≤3.3 and ≤11) at weeks 4, 8, 12, and 24 (TARGET) and week 52 (MOBILITY), and functional remission using the Health Assessment Questionnaire Disability Index (HAQ-DI; <0.5).
Compared with placebo, a higher proportion of sarilumab-treated patients on the MOBILITY and TARGET trials achieved remission (DAS28-CRP) and LDA (all criteria). In most patient groups, remission and LDA were achieved early, between weeks 4 and 8. Notably, continued sarilumab treatment (both doses) resulted in additional patients achieving remission and LDA at subsequent time points through week 24, with additional patients achieving remission between weeks 24 and 52 (MOBILITY). In both sarilumab-treated groups in MOBILITY, normalization of physical function by HAQ-DI <0.5 was apparent by week 12 (nominal P <.05 vs placebo, both doses). In the TARGET trial, sarilumab-treated patients showed a small numeric difference in HAQ-DI normalization at all time points, which did not achieve nominal significance.
This post-hoc analysis of the MOBILITY and TARGET studies showed that patients treated with sarilumab achieved responses as early as week 4, and that ongoing sarilumab treatment resulted in achievement of remission or LDA through week 24, with additional increases seen through week 52 (MOBILITY) in patients with RA and inadequate response to MTX and inadequate response to, or intolerance of, TNF inhibitors.
Genovese MC, et al. ACR 2017. Abstract 2480.