title: Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes.
abstract: OBJECTIVE
  Blocking interleukin-1 with anakinra in patients with the autoinflammatory syndrome neonatal-onset multisystem inflammatory disease (NOMID) reduces systemic and organ-specific inflammation. However, the impact of long-term treatment has not been established. This study was undertaken to evaluate the long-term effect of anakinra on clinical and laboratory outcomes and safety in patients with NOMID.
  
  
  METHODS
  We conducted a cohort study of 26 NOMID patients ages 0.80-42.17 years who were followed up at the NIH and treated with anakinra 1-5 mg/kg/day for at least 36 months. Disease activity was assessed using daily diaries, questionnaires, and C-reactive protein level. Central nervous system (CNS) inflammation, hearing, vision, and safety were evaluated.
  
  
  RESULTS
  Sustained improvements in diary scores, parent's/patient's and physician's global scores of disease activity, parent's/patient's pain scores, and inflammatory markers were observed (all P<0.001 at 36 and 60 months). At 36 and 60 months, CNS inflammation was suppressed, with decreased cerebrospinal fluid white blood cell counts (P=0.0026 and P=0.0076, respectively), albumin levels, and opening pressures (P=0.0012 and P<0.001, respectively). Most patients showed stable or improved hearing. Cochlear enhancement on magnetic resonance imaging correlated with continued hearing loss. Visual acuity and peripheral vision were stable. Low optic nerve size correlated with poor visual field. Bony lesions progressed. Adverse events other than viral infections were rare, and all patients continued to receive the medication.
  
  
  CONCLUSIONS
  These findings indicate that anakinra provides sustained efficacy in the treatment of NOMID for up to 5 years, with the requirement of dose escalation. Damage progression in the CNS, ear, and eye, but not bone, is preventable. Anakinra is well tolerated overall.
authors.affiliation: Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
authors.forename: Cailin H
authors.initials: CH
authors.lastname: Sibley
authors.forename: Nikki
authors.initials: N
authors.lastname: Plass
authors.forename: Joseph
authors.initials: J
authors.lastname: Snow
authors.forename: Edythe A
authors.initials: EA
authors.lastname: Wiggs
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.forename: Kelly A
authors.initials: KA
authors.lastname: King
authors.forename: Christopher
authors.initials: C
authors.lastname: Zalewski
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Kim
authors.forename: Rachel
authors.initials: R
authors.lastname: Bishop
authors.forename: Suvimol
authors.initials: S
authors.lastname: Hill
authors.forename: Scott M
authors.initials: SM
authors.lastname: Paul
authors.forename: Patrick
authors.initials: P
authors.lastname: Kicker
authors.forename: Zachary
authors.initials: Z
authors.lastname: Phillips
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Dolan
authors.forename: Brigitte
authors.initials: B
authors.lastname: Widemann
authors.forename: Nalini
authors.initials: N
authors.lastname: Jayaprakash
authors.forename: Frank
authors.initials: F
authors.lastname: Pucino
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Stone
authors.forename: Dawn
authors.initials: D
authors.lastname: Chapelle
authors.forename: Christopher
authors.initials: C
authors.lastname: Snyder
authors.forename: John A
authors.initials: JA
authors.lastname: Butman
authors.forename: Robert
authors.initials: R
authors.lastname: Wesley
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002097:C-Reactive Protein; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D002097:C-Reactive Protein