Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously [SC] every 2 weeks [q2w]) plus conventional synthetic (cs)DMARDs demonstrated efficacy in adults with active, moderate‑to-severe RA and inadequate response or intolerance to TNF inhibitors. Consistent with IL-6 inhibition and the safety profile of SC sarilumab, infections, neutropenia, injection site reactions, increased lipids, and increased transaminases were among the most common treatment-emergent adverse events. The objective of this analysis was to examine whether patients who achieved clinical response and improvements in physical function at week 12 in TARGET continued to sustain response up until the end of study at week 24.

Methods: A sustained response was defined as a response at week 12 (see below) with continuous response until the end of the study. An additional definition of a sustained response allowed for a single visit in between without a response, with the exception of the last 2 visits. Patients were seen at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24 of the study. The sustainability of the response was measured for the following clinical efficacy endpoints: ACR20/50/70 response, HAQ–Disability Index (HAQ-DI; ≥0.22 units of improvement from baseline), clinical disease activity index (CDAI; ≤2.8 [remission], >2.8 to ≤10 [low disease activity; LDA]), simplified disease activity index (SDAI; ≤3.3 [remission], >3.3 to ≤11 [LDA]), and DAS28-CRP (<2.6, ≥2.6 to ≤3.2).

Results: A significantly higher percentage of patients treated with sarilumab + csDMARDs achieved ACR20/50/70 response (both doses) and HAQ-DI ≥0.22 units of improvement from baseline (200 mg q2w dose only) at week 12 in TARGET vs those treated with placebo + csDMARDs (Table). The majority of patients treated with sarilumab who achieved a response at week 12 sustained that response, or had up to 1 nonresponse, until the end of the study (Table). In contrast, there were fewer patients in the placebo + csDMARDs group who achieved and sustained a response from week 12 to the end of the study. These observations were similar regardless of whether a patient maintained a response at every visit after week 12 through the end of the study or had 1 nonresponse at a visit in between. A similar trend was also observed for CDAI and SDAI remission and LDA, and DAS28-CRP <2.6 and ≥2.6 to ≤3.2.

Conclusion: More patients with active, moderate-to-severe RA and inadequate response or intolerance to TNF inhibitors who were treated with sarilumab + csDMARDs achieved and sustained a clinically significant response compared with those treated with placebo + csDMARDs.