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)

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

Abstract: Objectives To assess the effi cacy 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 effi cacy 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 defi ned 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 effi cacy assessment for 12 months, and analyses of treatment effect on blood gene expression profi ling. 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 effi cacy (n=2) or a disease fl are (n=2). Blood gene expression profi ling 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 profi les in clinical responders and induces a de novo IFN signature. Trial Registration Number: NCT00339157.