title: Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial.
abstract: OBJECTIVE
  In juvenile idiopathic arthritis (JIA), the efficacy of very early disease-modifying drug therapy, synthetic or biological, is not well known. Three alternative strategies were compared for treating recent-onset polyarticular JIA.
  
  
  METHODS
  In a 54-week multicentre open-label clinical trial, 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4-15 years were randomly assigned into three treatment arms. The efficacy of infliximab plus methotrexate (TNF) was compared to that of two synthetic therapies: methotrexate alone (MTX) and DMARD methotrexate, sulphasalazine and hydroxychloroquine in combination (COMBO). Primary endpoint was American College of Rheumatology paediatric 75% improvement (ACR Pedi 75). Secondary endpoints were inactive disease and safety.
  
  
  RESULTS
  In 59 patients, mean (±SE) age at baseline was 9.6±0.4 years, duration of JIA 1.9±0.2 months and number of active joints 18±1. ACR Pedi 75 was achieved in 100% (19/19) of patients receiving TNF, 65% (13/20) on COMBO (95% CI 44% to 86%) and 50% (10/20) on methotrexate (95% CI 28% to 72%) p<0.0001. Thirteen patients receiving TNF (68%; 95% CI 47% to 89%) achieved inactive disease, whereas eight (40%; 95% CI 22% to 63%) on COMBO and five (25%; 95% CI 6% to 44%) on methotrexate did (p=0.002). Patients on TNF spent a mean 26 weeks (95% CI 18 to 34) with inactive disease, longer than did those receiving COMBO (13 weeks; 95% CI 6 to 20), or methotrexate (6 weeks; 95% CI 2 to 10). Serious adverse events were rare.
  
  
  CONCLUSIONS
  In early polyarticular JIA, targeting to achieve minimally active or inactive disease, infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone.
authors.affiliation: Department of Pediatric Rheumatology, Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland. pirjo.tynjala@hus.fi
authors.forename: Pirjo
authors.initials: P
authors.lastname: Tynjälä
authors.forename: Paula
authors.initials: P
authors.lastname: Vähäsalo
authors.forename: Maarit
authors.initials: M
authors.lastname: Tarkiainen
authors.forename: Liisa
authors.initials: L
authors.lastname: Kröger
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aalto
authors.forename: Merja
authors.initials: M
authors.lastname: Malin
authors.forename: Anne
authors.initials: A
authors.lastname: Putto-Laurila
authors.forename: Visa
authors.initials: V
authors.lastname: Honkanen
authors.forename: Pekka
authors.initials: P
authors.lastname: Lahdenne
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004812:Epidemiologic Methods; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D007270:Injections, Intra-Articular; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D012460:Sulfasalazine / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D004338:Drug Combinations; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D000069285:Infliximab; D008727:Methotrexate