Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. In the phase 3, 52-week MOBILITY study (NCT01061736), sarilumab (150 or 200 mg subcutaneously every 2 weeks [q2w]) + MTX demonstrated clinical and radiographic efficacy in adults with active, moderate-to-severe RA and inadequate response to MTX.¹ The most common treatment-emergent adverse events were infections, neutropenia, injection site reactions, and increased transaminases. The objective of this analysis was to examine differences in the mean duration of response based on various definitions of response in MOBILITY.

Methods: Patients who achieved a response at any point during the study were considered responders and included in these analyses. If patients had a missing value or took rescue medication, they were considered nonresponders for those specific visits. Patients who did not respond at any visit were excluded from analysis. Five different definitions of duration of response were used: (1) first response to loss of response (time from initial response to loss of response); (2) longest response (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 (cumulative number of weeks during which a patient was a responder, excluding nonresponder weeks in between responder weeks); (4) responder weeks percent (percentage of weeks during which a patient was a responder, excluding nonresponder weeks in between responder weeks); and (5) sustained response (binary analysis [yes/no] of whether the response was maintained until the end of the double-blind period). Duration of response was measured for ACR20, improvement in HAQ–Disability Index (HAQ-DI) of ≥0.3 units, clinical disease activity index (CDAI; ≤2.8), simplified disease activity index (SDAI; ≤3.3), and DAS28-CRP (<2.6).

Results: In patients achieving a response at any point in MOBILITY, those treated with sarilumab 150 or 200 mg q2w + MTX had significantly longer duration of response vs those treated with placebo + MTX regardless of definition of response used for ACR20, HAQ-DI, and DAS28-CRP (Table 1). Sarilumab-treated patients achieved significantly longer sustained response by both ACR20 and HAQ-DI, whether they achieved response at week 12 or 24 (Table 2).

Conclusion: This analysis examined 5 different definitions of clinical response. Regardless of definition of response used, patients treated with either dose of sarilumab + MTX experienced longer duration of response vs those treated with placebo + MTX.

Reference:

1. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437.