Quartier P, Allantaz F, Cimaz R, et al. 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)

Université Paris-Descartes and Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
Annals of the rheumatic diseases (Impact Factor: 10.38). 12/2010; 70(5):747-54. DOI: 10.1136/ard.2010.134254
Source: PubMed


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

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    • "Human recombinant IL-1 receptor antagonist (IL-1ra) can block the IL-1 mediated effects, and restore the balance of Th17/Treg cells. Even though the exact mechanisms remain largely unknown, the use of anakinra, an IL-1ra, as a therapy in RA was effective and safe (39). Treg cells highly express CTLA-4, which controls the suppressive function of Treg cells (40). "
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    • "The first indication that IL-1 blockade may be promising in children with sJIA was provided by Verbsky and White, who successfully treated two children with anakinra [62]. Since then, multiple additional case series have confirmed its effectiveness [63-65], as have RCTs of all three agents [39,44,46]. Anakinra appears to be of greater benefit to the systemic, rather than the articular, features of sJIA when not used at disease onset/diagnosis [64,65]; this topic will be discussed further below. "
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