Sarilumab Efficacy, Safety Comparable Among RA Patient Subgroups
WASHINGTON, DC—The IL-6Rα-targeting human mAb sarilumab exhibits comparable efficacy and safety for different patient subgroups in rheumatoid arthritis (RA), according to an analysis of data pooled from the Phase 3 TARGET and MOBILITY clinical studies, presented at the 2016 ACR/ARHP Annual Meeting.
Sarilumab's superiority to placebo was “generally consistent across patient subgroups,” reported lead study author Mark C. Genovese, MD, of the Stanford University Medical Center in Palo Alto, CA.
Efficacy and safety data for a total of 1,743 adult study participants were included in the analysis across pre-specified patient subgroups. In the MOBILITY study, sarilumab plus methotrexate (MTX) demonstrated efficacy among patients for whom MTX yielded inadequate RA responses. Sarilumab plus conventional synthetic DMARDs demonstrated efficacy in patients with inadequate response or intolerance to tumor necrosis factor (TNF) inhibitors.
Treatment effects were measured as ACR20 response at Week 24 and changes in HAQ-Disability Index (HAQ-DI) at Week 12, DAS28-CRP at Week 24, and clinical disease activity index (CDAI) at Week 24. Effects were assessed for patients receiving placebo (n=579), sarilumab 150mg every 2 weeks (n=581), and sarilumab 200mg every 2 weeks (n=583) across pre-specified subgroups. The researchers found that effects were smaller for the small number of patients with baseline seronegativity for RF or anti-CCP auto-antibody, or patients with baseline weight of ≥100kg, particularly for sarilumab (150mg every 2 weeks).
“Superiority of both sarilumab doses vs. placebo was observed across all subgroups except baseline RF status, anti-CCP autoantibody status, and weight,” reported Dr. Genovese. “A smaller treatment effect for sarilumab 150mg every 2 weeks was observed in RF and anti-CCP seronegative patients and those weighing ≥100kg for ACR20 and DAS28-CRP.”
ACR20 at Week 24 was 0.699 stratified by sex (male, female); 0.531 when stratified by race (white, all other races); 0.269 by age group (<65 years, ≥65 years); 0.592 by smoking history (yes, no); and 0.495 by RA duration (≤3, >3 to ≤10, >10 years).
Treatment-emergent adverse events (TEAEs) and serious AEs were more frequent with patients receiving sarilumab than placebo, and included infections, neutropenia, injection side reactions, and elevated transaminases. Serious infections were not associated with neutrophil reductions, the authors noted.
Several coauthors are employees of Sanofi Genzyme, which is developing sarilumab.