title: A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial).
abstract: BACKGROUND
  Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Children with JIA are at risk of inflammation of the uvea in the eye (uveitis). Overall, 20% to 25% of paediatric uveitis is associated with JIA. Major risk factors for development of uveitis in JIA are oligoarticular pattern of arthritis, an age at onset of arthritis of less than seven years of age, and antinuclear antibody positivity. In the initial stages of mild to moderate inflammation the uveitis is asymptomatic. This has led to current practice of screening all children with JIA for uveitis. Approximately 12% to 38% of patients with JIA develop uveitis in seven years following onset of arthritis. In 30% to 50% of children with JIA-associated uveitis structural complications are present at diagnosis. Furthermore about 50% to 75% of those with severe uveitis will eventually develop visual impairment secondary to ocular complications such as cataract and glaucoma. Defining the severity of inflammation and structural complications in uveitis patients is now possible following Standardised Uveitis Nomenclature (SUN) guidelines, and modified to incorporate the consensus of end point and outcome criteria into the design of randomised trials. Despite current screening and therapeutic options (pre-biologics) 10% to 15% of children with JIA-associated uveitis may develop bilateral visual impairment and certified legally blind. To date, there remains no controlled trial evidence of benefits of biologic therapy.
  
  
  METHODS
  This study will randomise 154 patients aged 2 to 18 years with active JIA-associated uveitis (despite methotrexate (MTX) treatment for at least 12 weeks). All participants will be treated for 18 months, with follow up of 3 years from randomisation (continuing on MTX throughout). All participants will receive a stable dose of MTX and in addition either adalimumab (20 mg/0.8 ml for patients<30 kg or 40 mg/0.8 ml for patients weighing 30 kg or more, subcutaneous (s/c) injection every 2 weeks based on body weight), or placebo (0.8 ml as appropriate according to body weight) s/c injection every 2 weeks.
  
  
  CONCLUSIONS
  This is the first randomised controlled trial that will assess the clinical effectiveness, safety and cost effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis.
  
  
  BACKGROUND
  ISRCTN10065623.
authors.affiliation: University Hospitals Bristol NHS Foundation Trust, Upper Maudlin Street, Bristol BS2 8HW, UK. avramanan@hotmail.com.
authors.forename: Athimalaipet V
authors.initials: AV
authors.lastname: Ramanan
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Dick
authors.forename: Diana
authors.initials: D
authors.lastname: Benton
authors.forename: Sandrine
authors.initials: S
authors.lastname: Compeyrot-Lacassagne
authors.forename: Dalia
authors.initials: D
authors.lastname: Dawoud
authors.forename: Ben
authors.initials: B
authors.lastname: Hardwick
authors.forename: Helen
authors.initials: H
authors.lastname: Hickey
authors.forename: Dyfrig
authors.initials: D
authors.lastname: Hughes
authors.forename: Ashley
authors.initials: A
authors.lastname: Jones
authors.forename: Patricia
authors.initials: P
authors.lastname: Woo
authors.forename: Clive
authors.initials: C
authors.lastname: Edelsten
authors.forename: Michael W
authors.initials: MW
authors.lastname: Beresford
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D004359:Drug Therapy, Combination; D006801:Humans; D008131:London; D008727:Methotrexate / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014605:Uveitis / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000209:etiology
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D000068879:Adalimumab; D008727:Methotrexate