title: Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome.
abstract: OBJECTIVE
  Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is the most severe phenotype, with fever, rash, articular manifestations, and neurologic and neurosensory involvement. CAPS are caused by mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been shown to be an effective treatment; however, data on long-term efficacy and safety have been sparse. This study was undertaken to assess the long-term efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome.
  
  
  METHODS
  We retrospectively analyzed the medical records of NOMID/CINCA syndrome patients referred to 2 centers, who had started anakinra treatment before June 2007.
  
  
  RESULTS
  There were 10 patients with NOMID/CINCA syndrome who had been treated with anakinra. The patients' ages at the time anakinra treatment was initiated ranged from 3 months to 20 years. They had been followed up for 26-42 months. Sustained efficacy in the treatment of systemic inflammation and, in some cases, neurologic involvement and growth parameters, was achieved. The dosage of anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous system inflammation and deafness persisted in some patients, especially if there had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in cases in which it was present at treatment initiation, but no new lesions developed. No effect on overgrowth arthropathy was observed. Adverse events consisted of mild injection-site reactions.
  
  
  CONCLUSIONS
  The present results indicate that anakinra treatment is effective over the long term in NOMID/CINCA syndrome. However, treatment has to be initiated before irreversible lesions develop, and, particularly in very young patients, dosage adjustment is required.
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, INSERM U768, Université René Descartes-Paris 5, Paris, France. benedicte.neven@nck.aphp.fr
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marvillet
authors.forename: Celine
authors.initials: C
authors.lastname: Terrada
authors.forename: Alice
authors.initials: A
authors.lastname: Ferster
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Vincent
authors.initials: V
authors.lastname: Couloignier
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinto
authors.forename: Anne
authors.initials: A
authors.lastname: Pagnier
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.forename: Bahram
authors.initials: B
authors.lastname: Bodaghi
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Prieur
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
mesh_terms: D000293:Adolescent; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D003638:Deafness / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004660:Encephalitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D012189:Retrospective Studies; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein