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.