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).

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 enrollment 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.

• Authors: Pierre Quartier, Florence Allantaz, Rolando Cimaz, Pascal Pillet, Claude Messiaen, Christophe Bardin, Xavier Bossuyt, Anne Boutten, Jacques Bienvenu, Agnes Duquesne, Olivier Richer, Damien Chaussabel, Agnes Mogenet, Jacques Banchereau, Jean-Marc Treluyer, Paul Landais, Virginia Pascual
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 70 Issue 5 Pg. 747-54 (May 2011) ISSN: 1468-2060 [Electronic] England
• PMID: 21173013 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 23-valent pneumococcal capsular polysaccharide vaccine
• Antibodies, Bacterial
• Antirheumatic Agents
• Biomarkers
• Interleukin 1 Receptor Antagonist Protein
• Pneumococcal Vaccines
• Polysaccharides, Bacterial
• C-Reactive Protein

Topics

• Adolescent
• Antibodies, Bacterial (biosynthesis)
• Antirheumatic Agents (adverse effects, therapeutic use)
• Arthritis, Juvenile (blood, drug therapy, genetics, immunology)
• Biomarkers (blood)
• Blood Sedimentation
• C-Reactive Protein (metabolism)
• Child
• Child, Preschool
• Double-Blind Method
• Female
• Gene Expression Profiling (methods)
• Humans
• Interleukin 1 Receptor Antagonist Protein (adverse effects, therapeutic use)
• Male
• Pneumococcal Vaccines (immunology)
• Polysaccharides, Bacterial (immunology)
• Severity of Illness Index
• Treatment Outcome
• Young Adult