Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. Sarilumab (150 or 200 mg every 2 weeks [q2w] subcutaneously) + MTX demonstrated efficacy vs placebo in patients with RA and inadequate response to MTX (MOBILITY; NCT01061736),¹ and sarilumab (150 or 200 mg q2w) + conventional synthetic DMARDs demonstrated efficacy vs placebo in patients with RA and inadequate response to or intolerance of TNF inhibitors (TARGET; NCT01709578).² In both studies, the most common treatment-emergent adverse events (TEAEs) included infections, neutropenia, injection site reactions, and increased transaminases.^1,2 In this pooled exploratory analysis, safety and efficacy of sarilumab were examined in patients <65 and ≥65 years of age from MOBILITY and TARGET.

Methods: Safety and efficacy endpoints (Table) were analyzed in subgroups of patients <65 and ≥65 years. A logistic regression model was used to analyze ACR20 and DAS28-CRP <2.6 responses, and a mixed-effect model for repeated measures was used for HAQ-Disability Index (HAQ-DI), DAS28-CRP, and clinical disease activity index (CDAI).

Results: In both subgroups, most patients were female (80%-82%). In patients ≥65 years, mean RA duration was longer (13.2 vs 9.5 years) and a higher proportion had prior biologic use (63% vs 48%) vs those <65 years. In both subgroups, incidence of TEAEs and serious AEs (SAEs) was greater in sarilumab-treated patients vs placebo. Infections were the most common TEAEs with sarilumab in both age groups. Incidence of SAEs, including serious infections, was higher in patients ≥65 years vs patients <65 years. In both subgroups, both sarilumab doses vs placebo led to numerically higher ACR20 and DAS28-CRP <2.6 response rates at week 24, improvement from baseline in HAQ-DI at week 12, and improvement from baseline in DAS28-CRP and CDAI at week 24 (Table). In general, efficacy of sarilumab 150 and 200 mg q2w was comparable between patients ≥65 years and <65 years. There was some variability in the proportion of patients >65 years who achieved ACR20 and DAS28-CRP <2.6 responses due to the small number of patients in this subgroup; however, the age-by-treatment interaction was not significant for any of the efficacy endpoints (P>0.2).

Conclusion: Adverse events in both age groups were consistent with the known safety profile of sarilumab. SAEs occurred more frequently in patients ≥65 years compared with patients <65 years, consistent with other studies of biologic agents in the elderly.³ Both sarilumab doses were superior to placebo in ACR20 and DAS28-CRP <2.6 responses, DAS28-CRP, and CDAI at week 24 and in change from baseline in HAQ-DI at week 12 in both subgroups defined by age. References: 1. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437. 2. Fleischmann et al. Presented at: ACR; November 7-11, 2015; San Francisco, CA. 3. Ishchenko et al. Drugs Aging. 2016;33:387-398.