Background Sarilumab (SAR) is a fully human mAb directed against IL-6Rα.
Objectives Evaluate the temporal pattern of cumulative incidence of ACR50 and EULAR (good+moderate) responses during the MOBILITY Part A study.
Methods Adults with active, moderate-to-severe RA and an inadequate response to treatment with MTX were randomized to 6 groups: SAR 100mg every other week (q2w), 150mg q2w, 100mg weekly (qw), 20 mg q2w, 150mg qw, or placebo (Pbo). All patients (pts) were on background MTX. Kaplan-Meier and proportional hazards methods were used to evaluate cumulative incidence of pts achieving ACR50 response during first 12 wks. Similar analyses were conducted for EULAR responses based on proportion by week and time to event comparing EULAR good+moderate response for all 6 groups.
Results Baseline demographic and disease characteristics were similar across treatment groups (n=306): 79% women; mean age 52 yrs; disease duration 8 yrs; RF+ 79.7%; tender joint count 27; swollen joint count 17; hsCRP 2.8mg/dL; HAQ-DI 1.6. In contrast to Pbo and 100 q2w groups, 4 SAR doses showed a response to treatment by wk 2. The 25th percentile was achieved on or before wk 8 in 150 and 200mg q2w groups and in 100 and 150 qw groups. Table 1 shows relative hazards for achieving ACR50 response in sari vs Pbo. EULAR response results confirm ACR 50 response with 4 SAR groups (all except 100mg q2w) achieving significantly higher proportions of EULAR good and EULAR good+moderate responses vs Pbo by wk 2. Observed AEs were similar to those reported with other IL-6 inhibitors.
Conclusions The effect of SAR in reducing signs and symptoms by the ACR50 response and EULAR good and good+moderate criteria was seen early. Pts treated with 150 or 200mg q2w or 100 or 150mg qw were >2 times as likely as Pbo to achieve ACR50 response after 12 wks. A significant improvement in the proportion of EULAR responders was also observed for 4 SAR groups starting at wk 2. These proportional hazard methods support Phase 3 study of 150 and 200mg q2w regimens that provide high hurdle ACR and EULAR clinical responses.
Acknowledgements Funded by Sanofi and Regeneron.
Disclosure of Interest R. Fleischmann Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron, S. Fiore Employee of: Sanofi, C. Fan Employee of: Sanofi, D. Thompson Employee of: Regeneron