Efficacy and Safety of Firsekibart in Treatment of Active Systemic Juvenile Idiopathic Arthritis: A Randomized Phase 2 Study

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disorder that impacts children aged ≤ 16 years. This study evaluated the efficacy and safety of firsekibart, a fully human anti-IL-1β monoclonal antibody, in children with active sJIA. METHODS: This multicenter, randomized, open-label, active-controlled phase 2 study (NCT05925452) enrolled participants aged 2- < 18 years with active sJIA across 14 sites in China. Participants were randomized (1:1:1) to firsekibart 3.0 mg/kg or 4.0 mg/kg subcutaneously every 4 weeks, or tocilizumab intravenously every 2 weeks, for 24 weeks. The primary endpoint was modified JIA American College of Rheumatology Pediatric criteria (ACR Pedi) 30 response at day 28. Secondary endpoints included ACR Pedi 30/50/70/90 responses, corticosteroid tapering, immunogenicity, and safety. RESULTS: Fifty participants were randomized (firsekibart 3.0 mg/kg: n = 17; 4.0 mg/kg: n = 16; tocilizumab: n = 17). At day 28, ACR Pedi 30 response rates were 94.1% (95% CI 71.3-99.9), 75.0% (47.6-92.7) and 82.4% (56.6-96.2) in the firsekibart 3.0 mg/kg, 4.0 mg/kg, and tocilizumab groups, respectively. Firsekibart 3.0 mg/kg achieved numerically higher ACR Pedi 70/90 responses. By the end of treatment, successful corticosteroid tapering occurred in 75.0%, 63.6%, and 62.5% of patients receiving firsekibart 3.0 mg/kg, 4.0 mg/kg, and tocilizumab, respectively. No MAS events or anti-drug or neutralizing antibodies were detected. Treatment-emergent adverse events (TEAEs) occurred in 70.6%, 93.8%, and 94.1% of participants in the firsekibart 3.0 mg/kg, 4.0 mg/kg, and tocilizumab groups, respectively. Grade ≥ 3 TEAEs were absent in the 3.0 mg/kg group. Common TEAEs mainly included infections and laboratory abnormalities. CONCLUSIONS: Firsekibart demonstrated rapid clinical improvement, steroid-sparing effects, and an acceptable safety profile. The 3.0 mg/kg dose provided the most favorable benefit-risk balance, with efficacy and safety outcomes comparable to tocilizumab, supporting further evaluation as a convenient once-every-4-weeks IL-1β-targeted option in future phase 3 trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05925452.