Dr. Ruperto has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers Squibb, Roche, Novartis, Wyeth/Pfizer, and AstraZeneca (less than $10,000 each).
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†
Article first published online: 27 JAN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 2, pages 557–567, February 2012
How to Cite
Ruperto, N., Quartier, P., Wulffraat, N., Woo, P., Ravelli, A., Mouy, R., Bader-Meunier, B., Vastert, S. J., Noseda, E., D'Ambrosio, D., Lecot, J., Chakraborty, A., Martini, A., Chioato, A. and Paediatric Rheumatology International Clinical Trials Organisation (2012), 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. Arthritis & Rheumatism, 64: 557–567. doi: 10.1002/art.33342
EudraCT database no. 2006-001834-42.
- Issue published online: 27 JAN 2012
- Article first published online: 27 JAN 2012
- Accepted manuscript online: 27 SEP 2011 10:26AM EST
- Manuscript Accepted: 6 SEP 2011
- Manuscript Received: 9 JUN 2011
- Novartis Pharma, Basel, Switzerland
- Paediatric Rheumatology International Clinical Trials Organisation (PRINTO)
- Bristol-Myers Squibb
- Schwartz Biosciences
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.
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.
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.
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.