JIA is the most common rheumatic disease in children with up to 38% of children developing uveitis as a co-morbidity. Uveitis is inflammation of the uvea (the middle layer of the eye) with chronic uveitis causing eye complications including glaucoma and cataracts, which can ultimately lead to permanent vision loss. Up to 50% of children experience disease that is unresponsive to standard treatments, e.g. corticosteroids and methotrexate. Corticosteroids, the first-line treatment for uveitis, should be limited because the risk of developing cataract increases with more than three corticosteroid drops per day. Uveitis impacts on quality of life, with the burden of examinations and treatments, alongside the potential of becoming blind.
Working in partnership
In 2007 Professor Michael Beresford developed the UK's Paediatric Rheumatology Clinic Study Group, forming a unique partnership between the NIHR Medicines for Children Network and what is now Versus Arthritis. Their remit was to identify and tackle the major clinical priorities in paediatric rheumatic disorders in the UK and internationally. Tackling JIA-uveitis was identified as one of the top two priorities to address.
Professor Beresford jointly led the SYCAMORE Trial, which investigated the effectiveness of the drug adalimumab in the treatment of JIA-associated uveitis. The trial was halted 18 months early due to the very significant positive effect of adalimumab on disease remission.
The success of the SYCAMORE Trial enabled the researchers to secure funding from Arthritis Research UK (now Versus Arthritis) for the APTITUDE Trial of tocilizumab in JIA-associated uveitis patients whose condition was unresponsive to adalimumab and methotrexate.
The accomplishments of the University of Liverpool working in partnership with Alder Hey Children's NHS Foundation Trust and its national and international partners in paediatric rheumatology, led Professor Beresford to be successfully awarded the UK's first and only 'Experimental Arthritis Treatment Centre for Children' (EATC4Children). The EATC4Children includes colleagues in Bristol and Sheffield and was initially supported by Versus Arthritis, as well as the University of Liverpool, Alder Hey Children's NHS Foundation Trust and the Alder Hey Charity. Amongst its various key priority areas, SYCAMORE, APTITUDE and a succession of follow-on investigator-led and industry-sponsored studies forms part of the JIA-uveitis workstream of the EATC4Children, delivered in close partnership with colleagues in Bristol. Having launched in 2014, the funding for the EATC4Children was successfully renewed by Versus Arthritis in 2021 for a further three years.
SYCAMORE was the world's first randomised controlled trial in JIA-associated uveitis and led to rapid changes in drug commissioning policy. In 2015 the NHS revised its Clinical Commissioning Policy to recommend the use of adalimumab for children with severe refractory uveitis. The results of the SYCAMORE trial have been used for commercial licensing across Europe and North America, through the European Medicines Agency (2017), the Food and Drug Administration - FDA (2018) and Health Canada (2019). This has resulted in approval of adalimumab for the indication of non-infectious uveitis (JIA- and non-JIA-associated) across 65 countries and international access to this sight-saving therapy.
Data from NHS England alone reports 315 children have been prescribed adalimumab for JIA-associated uveitis since the Commissioning Policy in November 2015. Another 166 children received the drug for non-JIA-associated non-infectious anterior uveitis, highlighting an additional patient population benefiting from SYCAMORE. All these children may have lost their sight without this intervention. Globally, based on the prevalence of JIA-uveitis, some 50,000 children now have access to adalimumab for this condition.
The UK’s EATC4Children has been instrumental over the past six years, nationally and internationally, in tackling major inflammatory conditions affecting children and young people.Professor Michael Beresford
Back to: Faculty of Health and Life Sciences