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Open Access Highly Accessed Study protocol

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)

Athimalaipet V Ramanan1*, Andrew D Dick2, Diana Benton1, Sandrine Compeyrot-Lacassagne3, Dalia Dawoud5, Ben Hardwick4, Helen Hickey4, Dyfrig Hughes5, Ashley Jones4, Patricia Woo3, Clive Edelsten3, Michael W Beresford4 and The SYCAMORE Trial Management Group

Author Affiliations

1 University Hospitals Bristol NHS Foundation Trust, Upper Maudlin Street, Bristol BS2 8HW, UK

2 Bristol Eye Hospital, Upper Maudlin Street, Bristol BS2 8HW, UK

3 Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK

4 University of Liverpool, Alder Hey Children’s NHS Foundation Trust, Eaton Road, Liverpool L12 2AP, UK

5 Bangor University, College Road, Bangor LL57 2DG, UK

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Trials 2014, 15:14  doi:10.1186/1745-6215-15-14

Published: 9 January 2014

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/design

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.

Discussion

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.

Trial registration

ISRCTN10065623

Keywords:
Adalimumab; Juvenile idiopathic arthritis; Methotrexate; Ophthalmology; Paediatric; Rheumatology; Safety; Uveitis