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)

Ann Rheum Dis. 2011 May;70(5):747-54. doi: 10.1136/ard.2010.134254. Epub 2010 Dec 20.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Bacterial / biosynthesis
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / 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
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Male
  • Pneumococcal Vaccines / immunology
  • Polysaccharides, Bacterial / immunology
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00339157