title: Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.
abstract: OBJECTIVE
  To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome.
  
  
  RESULTS
  Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed.
  
  
  CONCLUSIONS
  Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.
authors.affiliation: Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. pnigrovic@partners.org
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Melissa
authors.initials: M
authors.lastname: Mannion
authors.forename: Femke H M
authors.initials: FH
authors.lastname: Prince
authors.forename: Andrew
authors.initials: A
authors.lastname: Zeft
authors.forename: C Egla
authors.initials: CE
authors.lastname: Rabinovich
authors.forename: Marion A J
authors.initials: MA
authors.lastname: van Rossum
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cortis
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardeo
authors.forename: Paivi M
authors.initials: PM
authors.lastname: Miettunen
authors.forename: Ginger
authors.initials: G
authors.lastname: Janow
authors.forename: James
authors.initials: J
authors.lastname: Birmingham
authors.forename: Aaron
authors.initials: A
authors.lastname: Eggebeen
authors.forename: Erin
authors.initials: E
authors.lastname: Janssen
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Shulman
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Son
authors.forename: Sandy
authors.initials: S
authors.lastname: Hong
authors.forename: Karla
authors.initials: K
authors.lastname: Jones
authors.forename: Norman T
authors.initials: NT
authors.lastname: Ilowite
authors.forename: Randy Q
authors.initials: RQ
authors.lastname: Cron
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Higgins
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007391:International Cooperation; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D053590:Interleukin 1 Receptor Antagonist Protein; D002097:C-Reactive Protein