A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features

Objective To assess dosing, preliminary safety, and efficacy of canakinumab, a fully human anti–interleukin‐1β (anti–IL‐1β) antibody, in children with systemic juvenile idiopathic arthritis (JIA) and active systemic features. Methods In this phase II, multicenter, open‐label, dosage‐escalation study, children with systemic JIA who were ≥4 years of age, had fever, and were receiving ≤0.4 mg/kg/day of corticosteroids were administered a single subcutaneous dose of canakinumab, 0.5–9 mg/kg of body weight, and were redosed upon relapse. Response to treatment was assessed according to an adaptation of the American College of Rheumatology (ACR) pediatric criteria for improvement. Results A total of 23 children ages 4–19 years with active disease were enrolled. Of these, 1 patient was excluded from analysis, and 3 of the reenrolled patients were included twice in the efficacy analysis. By day 15 of the first treatment cycle, 15 of 25 patients (60%) had achieved an adapted ACR Pediatric 50 response, with 4 of them achieving inactive disease status. Response was sustained over time, with 11 of 13 patients able to maintain their response throughout the study. In 8 of the 11 responders who had been receiving steroids at baseline, the steroid dosage was decreased from a mean of 0.38 mg/kg/day to 0.13 mg/kg/day over the first 5 months, and 4 of them were able to discontinue steroids. At a dose of 4 mg/kg of canakinumab given subcutaneously every 4 weeks, the median percentage of patients predicted to relapse within 4 weeks was estimated to be 6% (95% confidence interval 1–21). Therapy was generally well tolerated and few patients experienced injection‐site reactions. Conclusion Canakinumab has a promising preliminary safety and efficacy profile in this limited cohort. Based on the findings of this trial, further studies in a larger population of children with systemic JIA are warranted.