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

Authors

  • Nicolino Ruperto,

    Corresponding author
    1. IRCCS G. Gaslini, Genoa, Italy
    • Paediatric Rheumatology International Trials Organisation (PRINTO), IRCCS G. Gaslini, Università di Genova, Pediatria II—Reumatologia, Largo Gaslini 5, Genoa 16147, Italy
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    • 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).

  • Pierre Quartier,

    1. Université Paris Descartes and Hôpital Necker–Enfants Malades, AP-HP, Paris, France
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    • Dr. Quartier has received consulting fees, speaking fees, and/or honoraria from Novartis, Abbott, Pfizer, Bristol-Myers Squibb, Servier, Biovitrum, and Chugai-Roche (less than $10,000 each).

  • Nico Wulffraat,

    1. University Medical Centre, Utrecht, The Netherlands
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    • Dr. Wulffraat has received speaking fees from Novartis (less than $10,000).

  • Patricia Woo,

    1. University College London, London, UK
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    • Dr. Woo has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • Angelo Ravelli,

    1. IRCCS G. Gaslini and University of Genoa, Genoa, Italy
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    • Dr. Ravelli has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers Squibb, Novartis, and Roche (less than $10,000 each).

  • Richard Mouy,

    1. Université Paris Descartes and Hôpital Necker–Enfants Malades, AP-HP, Paris, France
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    • Dr. Mouy has received consulting fees, speaking fees, and/or honoraria from Novartis (less than $10,000).

  • Brigitte Bader-Meunier,

    1. Université Paris Descartes and Hôpital Necker–Enfants Malades, AP-HP, Paris, France
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    • Dr. Bader-Meunier has received consulting fees, speaking fees, and/or honoraria from Novartis and Abbott (less than $10,000 each).

  • Sebastiaan J. Vastert,

    1. University Medical Centre, Utrecht, The Netherlands
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  • Emanuele Noseda,

    1. Novartis Institute for Biomedical Research, Basel, Switzerland
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  • Daniele D'Ambrosio,

    1. Novartis Institute for Biomedical Research, Basel, Switzerland
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    • Drs. D'Ambrosio, Chakraborty, and Chioato own stock or stock options in Novartis.

  • Jean Lecot,

    1. Novartis Institute for Biomedical Research, Basel, Switzerland
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  • Abhijit Chakraborty,

    1. Novartis Institute for Biomedical Research, Basel, Switzerland
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  • Alberto Martini,

    1. IRCCS G. Gaslini and University of Genoa, Genoa, Italy
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    • Dr. Martini has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers Squibb, Novartis, AstraZeneca, and GlaxoSmithKline (less than $10,000 each).

  • Andrea Chioato,

    1. Novartis Institute for Biomedical Research, Basel, Switzerland
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  • Paediatric Rheumatology International Clinical Trials Organisation


  • EudraCT database no. 2006-001834-42.

Abstract

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.

Ancillary