217 Improvementsin remission and low disease activity are achieved with ongoing sarilumabtreatment, in patients with rheumatoid arthritis in two phase III studies

Abstract

Background: Sarilumab is a human mAb blocking the IL‐6Ra. Efficacy and safety of sarilumab (150 or 200mg subcutaneously every two weeks [q2w]) plus conventional synthetic (cs) DMARDs were demonstrated in patients with active, moderate‐to‐severe RA in two Phase III studies: the 52‐week MOBILITY study (NCT01061736) in patients with inadequate response to MTX (MTX‐IR) and the 24‐week TARGET study (NCT01709578) in patients with inadequate response to or intolerance of TNF inhibitors (TNF‐IR). The most common treatment‐emergent adverse events in both studies included infections, neutropenia, injection‐site reactions, and increased transaminases. This post‐hoc analysis assessed the proportion of patients who achieved treat‐to‐target goals of remission or low disease activity (LDA) by 1 year in MOBILITY and six months in TARGET. Methods: Adults with active RA were randomised 1:1:1 to receive sarilumab 150 or 200mg q2w or placebo plus background MTX (MOBILITY) or csDMARDs (TARGET). Clinical efficacy was evaluated for remission and LDA using 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 (and additionally at Week 52 in MOBILITY). Functional remission (HAQDisability Index [HAQ‐DI] <0.5) was also assessed. Results: In both studies, more sarilumab‐treated patients achieved remission (DAS28‐CRP only) and LDA (all criteria) versus placebo (Table). Although remission and LDA generally became evident between Weeks 4 and 8 in most patient groups (nominal P<0.05 vs placebo, both doses), additional patients achieved remission and LDA at each successive time point assessed through week 24 in both studies; and between weeks 24 and 52 in MOBILITY. Normalization of physical function (HAQ‐DI <0.5) was evident in sarilumab‐treated groups in MOBILITY by week 12 (nominal P<0.05 vs placebo, both doses); in TARGET, the numerical difference in HAQ‐DI normalization in favor of sarilumab didn't achieve nominal significance. Conclusion: In MTX‐IR and TNF‐IR patients with RA treated with sarilumab, efficacy became evident as early as week four. The numbers of patients who achieved remission or LDA increased through week 24 with ongoing sarilumab treatment in both studies, with further increases observed up to week 52 in MOBILITY. (Table Presented).