Article

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: 9.27). 12/2010; 70(5):747-54. DOI: 10.1136/ard.2010.134254
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
104 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Children and adolescents with inflammatory rheumatic diseases have a disease and treatment-related increased risk of infections. This risk includes vaccine-preventable diseases; therefore, vaccinations represent an important preventive measure against infection in these patients. However, approximately one in three patients with a juvenile rheumatic disease is nowadays still inadequately vaccinated, mostly due to uncertainty regarding the efficacy and safety of vaccination in these patients. This paper summarizes the available evidence regarding the efficacy and safety of vaccinations in children and adolescents with rheumatic diseases and gives recommendations for the clinical practice. Almost 2000 children and adolescents with rheumatic diseases were examined in the more than 30 previously published vaccination studies, comprising nearly all standard vaccinations in the immunization schedule. The immunogenicity was usually sufficient and there was no evidence of a relevant aggravation of the underlying disease. Recommendations for the clinical practice are given also considering data beyond pediatric rheumatology; however, a final benefit-risk assessment is not yet possible.
    Zeitschrift für Rheumatologie 12/2014; 73(10):878-89. DOI:10.1007/s00393-014-1396-x · 0.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adult-onset Still's disease (AOSD) is a rare inflammatory disorder that has been recently classified as a polygenic autoinflammatory disorder. The former classification, based on the disease course, seems to be quite dated. Indeed, there is accumulating evidence that AOSD can be divided into two distinct phenotypes based on cytokine profile, clinical presentation, and outcome, ie, a "systemic" pattern and an "articular" pattern. The first part of this review deals with the treatments that are currently available for AOSD. We then present the different strategies based on the characteristics of the disease according to clinical presentation. To do so, we focus on the two subsets of the disease. Finally, we discuss the management of life-threatening complications of AOSD, along with the therapeutic options during pregnancy.
    Therapeutics and Clinical Risk Management 01/2015; 11:33-43. DOI:10.2147/TCRM.S64951 · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite their limited licensed indications, anti-interleukin-1 (anti-IL-1) agents are often used in clinical practice for an increasing number of auto-inflammatory diseases. We conducted a national cross-sectional observational study from January 2011 to January 2013 to record the off-label use of such agents in France. We aimed to estimate the off-label use of anti-IL-1 treatments in France, assess their efficacy in rare diseases, and increase the reporting of their possible side effects. Physicians answered a questionnaire that covered patient and disease data, anti-IL-1 agent use, efficacy and adverse events. The study involved adult or paediatric patient who had received an anti-IL-1 agent after January 2005 in France. In total, 189 patients from 38 centres were included. The main diseases were adult-onset Still's disease (AOSD) (35), gout (28), systemic juvenile idiopathic arthritis (27), cryopyrin-associated periodic syndrome (CAPS) (21), familial Mediterranean fever (14) and mevalonate kinase deficiency (12). The main off-label used agent was anakinra, used at least once for 185 patients, with canakinumab used for 25. Anakinra was effective in most patients (90%), with higher complete clinical response rates for Schnitzler's syndrome, gout, CAPS and AOSD. Overall, 58% of patients showed at least one adverse event, mainly minor injection-site reactions. The main reported serious adverse event was severe infection. Injection-site reactions and liver toxicity were significantly more frequent in children than adults. The main non-cutaneous adverse event was liver toxicity, significantly associated with treatment duration. Weight gain was reported in about 10% of patients and was associated with treatment duration and CAPS. Canakinumab was rarely used and showed better cutaneous tolerance than anakinra but similar rates of non-cutaneous and severe adverse events. Anakinra was well tolerated and effective in most patients with various inflammatory diseases. The main adverse events were mild injection-site reactions, especially in children. The survey allowed for collecting limited information on the off-label use of canakinumab.
    Orphanet Journal of Rare Diseases 02/2015; 10(1):19. DOI:10.1186/s13023-015-0228-7 · 3.96 Impact Factor

Full-text (4 Sources)

Download
58 Downloads
Available from
Jun 1, 2014