Sarilumab, a human anti–interleukin-6R monoclonal antibody, is currently approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) in the United States. The phase 3 TARGET study demonstrated that sarilumab (150 or 200 mg subcutaneously every 2 weeks [q2w]) plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) achieved clinical responses in terms of RA signs and symptoms and physical function compared with placebo in adults with active, moderate–to-severe RA who were intolerant of, or showed inadequate response to, tumor necrosis factor (TNF) inhibitors. The co-primary end points of the TARGET trial were 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24 and change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at week 12. The current analysis determined whether a sustained response was achieved at week 24 in the TARGET study.
In this analysis, a sustained response was defined as a response at week 12 with continuous response until the end of the study (week 24); an alternative definition allowed for a single visit in between without a response, with the exception of the last 2 visits. Patients were evaluated at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24. Sustained response was measured for the following clinical efficacy end points and was defined as follows: ACR20 and 50%/70% improvement in ACR response criteria (ACR50/ACR70), HAQ-DI (≥0.22 units of improvement from baseline), Clinical Disease Activity Index (CDAI; ≤2.8 [remission], >2.8-≤10 [low disease activity; LDA]), Simplified Disease Activity Index (SDAI; ≤3.3 [remission], >3.3 to ≤11 [LDA]), and Disease Activity Score 28–C-reactive protein (DAS28-CRP; <2.6, ≥2.6-≤3.2).
This analysis included 181 patients randomized to placebo, 181 patients randomized to sarilumab 150 mg q2w, and 184 patients randomized to sarilumab 150 mg q2w. Baseline patient demographics and disease characteristics were balanced among TARGET treatment subgroups. Of the randomized patients, at week 12, a significantly higher percentage treated with both doses of sarilumab (150-mg or 200-mg doses) in combination with csDMARDs achieved ACR20 (sarilumab 150 mg, 54%; sarilumab 200 mg, 63%; placebo, 38%), whereas the sarilumab 200-mg q2w dose only resulted in HAQ-DI ≥0.22 units of improvement from baseline (sarilumab 150 mg, 48%; sarilumab 200 mg, 59%; placebo, 48%) at week 12 compared with placebo plus csDMARDs.
This analysis of the TARGET study showed that, at the end of the study (week 24), a greater proportion of ACR20 responders treated with sarilumab 150 mg (ACR20, 70.4%) or 200 mg (ACR20, 74.8%) at week 12 sustained that response (sarilumab 150 mg, 70%; sarilumab 200 mg, 75%; placebo, 57%), or had up to 1 nonresponse (sarilumab 150 mg, 77%; sarilumab 200 mg, 78%; placebo, 60%), whereas a lower proportion of those treated with placebo plus csDMARDs achieved and sustained a response. Similarly, HAQ-DI improvement ≥0.22 was sustained at all visits (sarilumab 150 mg, 67%; sarilumab 200 mg, 75%; placebo, 51%), or sustained with ≤1 nonresponse (sarilumab 150 mg, 68%; sarilumab 200 mg, 79%; placebo, 57%) at week 24. Other clinical end points assessed, including ACR50 and ACR70, CDAI and SDAI remission, LDA, and DAS28-CRP <2.6 and ≥2.6 to ≤3.2, also showed similar sustainability of responses with sarilumab versus placebo.
This analysis of the TARGET trial showed that a higher proportion of patients with active, moderate-to-severe RA and inadequate response to, or intolerance of, TNF inhibitors who were treated with sarilumab plus csDMARDs achieved and sustained a clinically significant response compared with those treated with placebo.
Fleischmann R, et al. ACR 2017. Abstract 2471.