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A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)
  1. Pierre Quartier1,
  2. Florence Allantaz2,
  3. Rolando Cimaz3,
  4. Pascal Pillet4,
  5. Claude Messiaen1,
  6. Christophe Bardin5,
  7. Xavier Bossuyt6,
  8. Anne Boutten7,
  9. Jacques Bienvenu8,
  10. Agnes Duquesne3,
  11. Olivier Richer4,
  12. Damien Chaussabel2,
  13. Agnes Mogenet1,
  14. Jacques Banchereau2,9,10,
  15. Jean-Marc Treluyer1,
  16. Paul Landais1,
  17. Virginia Pascual2
  1. 1Université Paris-Descartes and Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France
  2. 2Baylor Institute for Immunology Research, Dallas, Texas, USA
  3. 3Hôpital Femme-Mère-Enfant, Lyon, France
  4. 4Hôpital Pellegrin Enfants, Bordeaux, France
  5. 5Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, Paris, France
  6. 6University of Leuven, Leuven, Belgium
  7. 7Hôpital Xavier Bichat, Assistance Publique Hôpitaux de Paris, Paris, France
  8. 8Université Lyon Sud, Lyon, France
  9. 9INSERM Unit 899, Dallas, Texas, USA
  10. 10Mount Sinai School of Medicine, New York, New York, USA
  1. Correspondence to Dr Pierre Quartier, Unite d'Immuno-Hematologie et Rhumatologie Pediatriques, Hopital Necker-Enfants Malades, 149 rue de Sevres 75 015 Paris, France; pierre.quartier{at}nck.aphp.fr

Abstract

Objectives To assess the efficacy of the interleukin 1 receptor antagonist anakinra in systemic-onset juvenile idiopathic arthritis (SJIA).

Methods A multicentre, randomised, double-blind, placebo-controlled trial was conducted. The primary objective was to compare the efficacy of a 1-month treatment with anakinra (2 mg/kg subcutaneous daily, maximum 100 mg) with a placebo between two groups each with 12 patients with SJIA. Response was defined by a 30% improvement of the paediatric American College of Rheumatology criteria for JIA, resolution of systemic symptoms and a decrease of at least 50% of both C-reactive protein and erythrocyte sedimentation rate compared with baseline. After month 1 (M1), patients taking placebo were switched to anakinra. Secondary objectives included tolerance and efficacy assessment for 12 months, and analyses of treatment effect on blood gene expression profiling.

Results At M1, 8/12 responders were receiving anakinra and 1 responder receiving placebo (p=0.003). Ten patients from the placebo group switched to anakinra; nine were responders at M2. Between M1 and M12, six patients stopped treatment owing to an adverse event (n=2), lack of efficacy (n=2) or a disease flare (n=2). Blood gene expression profiling at enrolment and at 6 months' follow-up showed one set of dysregulated genes that reverted to normal values in the clinical responders and a different set, including interferon (IFN)-inducible genes, that was induced by anakinra.

Conclusions Anakinra treatment is effective in SJIA, at least in the short term. It is associated with normalisation of blood gene expression profiles in clinical responders and induces a de novo IFN signature.

Trial Registration Number: NCT00339157.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

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Footnotes

  • PL and VP contributed equally to this work.

  • Funding The promoter was the Institut Francais pour la Recherche Scientifique et Medicale (INSERM). Financial support was obtained from AMGEN (which had no role in analysis and reporting phase), INSERM, the French Society for Inflammatory Diseases in Pediatric Rheumatology (SOFREMIP), the Association for the Development of Pediatric Rheumatology (ADRI) and the French association for patients with Juvenile Arthritis KOURIR.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Necker-Enfants Malades Hospital, Paris, France, Commite pour la protection des personnes.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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