title: 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: OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT00339157.
authors.affiliation: Université Paris-Descartes and Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France. pierre.quartier@nck.aphp.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.forename: Florence
authors.initials: F
authors.lastname: Allantaz
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.forename: Pascal
authors.initials: P
authors.lastname: Pillet
authors.forename: Claude
authors.initials: C
authors.lastname: Messiaen
authors.forename: Christophe
authors.initials: C
authors.lastname: Bardin
authors.forename: Xavier
authors.initials: X
authors.lastname: Bossuyt
authors.forename: Anne
authors.initials: A
authors.lastname: Boutten
authors.forename: Jacques
authors.initials: J
authors.lastname: Bienvenu
authors.forename: Agnes
authors.initials: A
authors.lastname: Duquesne
authors.forename: Olivier
authors.initials: O
authors.lastname: Richer
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.forename: Agnes
authors.initials: A
authors.lastname: Mogenet
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Paul
authors.initials: P
authors.lastname: Landais
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D022242:Pneumococcal Vaccines / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D018501:Antirheumatic Agents; D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D002097:C-Reactive Protein