The efficacy and safety of sarilumab, a human monoclonal antibody blocking the interleukin-6 receptor alpha, was evaluated for treatment of rheumatoid arthritis (RA) in 3 clinical trials, including the MOBILITY trial. The phase 3, 52-week MOBILITY study demonstrated that subcutaneous sarilumab (150 mg or 200 mg every 2 weeks [q2w]) plus methotrexate (MTX) achieved clinical and radiographic efficacy in adults with active, moderate-to-severe RA and inadequate response to MTX. The current analysis examined differences in the mean duration of response in the MOBILITY study based on 5 different definitions of duration of response. The co-primary end points of the MOBILITY trial were proportion of patients achieving American College of Rheumatology (ACR) response at week 24, change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at week 16, and change from baseline in van der Heijde–modified total Sharp score at week 52.
The 5 different definitions of duration of response were: (1) first response to loss of response, defined as time from initial response to loss of response; (2) longest response, where all time segments of response were determined where each segment of response ended after first loss of response, and longest duration of response was selected; (3) responder weeks, defined as cumulative number of weeks during which a patient was a responder, excluding nonresponder weeks between responder weeks; (4) responder weeks percent, defined as percentage of weeks during which a patient was a responder, excluding nonresponder weeks between responder weeks; and (5) sustained response based on binary analysis (yes/no) of whether the response was maintained until the end of the double-blind period. Duration of response was measured for 20% improvement in American College of Rheumatology improvement criteria (ACR20), improvement in HAQ-DI of ≥0.3 units, Clinical Disease Activity Index (CDAI; ≤2.8), Simplified Disease Activity Index (SDAI; ≤3.3), and Disease Activity Score 28–C-reactive protein (DAS28-CRP; <2.6). Patients included in these analyses must have achieved a response at any point during the study and been considered responders. If patients had a missing value or took rescue medication, they were considered nonresponders for those specific visits.
The patient demographics and baseline disease characteristics were comparable between the treatment arms. Regardless of response definition used for ACR20, HAQ-DI, and DAS28-CRP, patients who achieved a response at any point with sarilumab 150 mg or 200 mg q2w plus MTX on the MOBILITY trial had significantly longer duration of response compared with those treated with placebo plus MTX. Whereas patients receiving sarilumab (150 mg or 200 mg) achieved numerically larger differences in CDAI and SDAI versus placebo; these differences did not reach a nominal P <.05. Compared with placebo, the number of responder weeks was also greater (nominal P <.0001) for patients who received sarilumab 150-mg and 200-mg treatment for ACR20 (61.0 and 65.0 vs 44.8%, respectively), HAQ-DI improvement (57.8 and 59.7 vs 44.4%, respectively), and DAS28-CRP (44.5 and 49.4 vs 29.4%, respectively). In terms of sustainability of response, significantly more sarilumab-treated patients showed responses by both ACR20 and HAQ-DI, regardless of whether they achieved response at week 12 or 24.
This analysis showed that patients treated with either dose of sarilumab plus MTX achieved longer duration of response versus those treated with placebo plus MTX, regardless of the definition of response used.
Genovese MC, et al. ACR 2017. Abstract 2479.