Impact case study database

The EATC4Children, under Professor Beresford’s leadership, has been instrumental in tackling sight-threatening JIA-associated uveitis in cases that were unresponsive to standard treatment, demonstrating the efficacy of the drug adalimumab through the SYCAMORE trial and enabling access to adalimumab for children across the globe.

Versus Arthritis describe the experience of one of many suffers that have benefitted, when other treatments were not working: **‘… for Lily, walking was too painful, and her sight was at risk when she was recruited to the SYCAMORE trial. Responding brilliantly to the treatment, she subsequently is ‘busy dancing, doing gymnastics, playing netball and spending time with her friends.’ [5.1]

Professor Beresford founded the UK’s Paediatric Rheumatology Clinic Study Group (CSG) in 2007, prioritising in its research strategy, sight-threatening JIA-associated uveitis. Under Professor Beresford’s leadership, the CSG established a proactive UK-wide Patient and Family Public Involvement and Engagement group (PPIE). Contributing directly to the CSG’s research strategy, PPIE directly contributed to SYCAMORE’s trial protocol development and the required final placebo-controlled study design, and all aspects of co-ordination and delivery. Recruiting centre clinicians note that families accepted and understood the importance and significance of the placebo design during trial recruitment: “The trial meant a lot to the children and the families who took part; I had not expected them to accept the placebo and understand why it was important.” [5.2]. This trial design ultimately contributed to the success and such a decisive outcome and impact of the trial.

Changing policy and practice

SYCAMORE was the world’s first randomised control trial in JIA-associated uveitis and led to rapid changes in drug commissioning policy; following the release of preliminary trial data in 2015, the NHS revised its Clinical Commissioning Policy of National Guidelines to provide access to adalimumab for children with severe refractory uveitis that same year [5.3]. Subsequently, the SYCAMORE trial was used specifically for commercial licensing across Europe and North America through the European Medicines Agency (2017), the Food and Drug Administration (2018) and Health Canada (2019) [5.3]. This 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 [5.1]. The international SHARE Initiative, endorsed by the worldwide Paediatric Rheumatology European Society, advocated for adalimumab use based on SYCAMORE in its recommendations for treatment of JIA-associated uveitis [5.4].

Benefits for patients

Adalimumab is prescribed in cases that are unresponsive to standard treatment and data from NHS England reports 315 children have been prescribed adalimumab for JIA-associated uveitis since the Commissioning Policy in November 2015 [5.5]. 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 indication. In 2017, Professors Beresford and Ramanan were awarded the University of Bristol Health and Wellbeing Impact Award (2017) for their seminal work in facilitating international access to adalimumab for children with uveitis [5.6].

Public and patient engagement

The SYCAMORE Trial has been widely disseminated to the public. BBC Radio 4’s “Inside Health’ featured it in 2017 [5.7]. Olivia’s Vision, the UK’s leading uveitis charity, responding to the NICE Multiple Technology Appraisal for treatment of non-infectious uveitis, explicitly referenced the importance of SYCAMORE [5.8]. Arthritis Research UK’s CEO highlighted SYCAMORE as one of the charity’s biggest achievements over the last 30 years describing it as “ a great example of the growing legacy of the TNF story, and how other biologic treatments can and are being used to effectively treat conditions” [5.9]. These examples highlight the importance of SYCAMORE for major charities and the patients they represent.

International drug licencing driving cultural change and economic impact

This publicly-funded trial was the first of its kind to secure a licensing contract with a commercial company, AbbVie, resulting in a submission to regulatory bodies. SYCAMORE established a UK-wide network of centres with joint paediatric rheumatology/ophthalmology multi-disciplinary clinics enhancing clinical care and enabling research. This UK-wide paediatric uveitis “trial culture” did not exist before SYCAMORE but led to successful delivery of APTITUDE. The EATC4Children has subsequently secured a pipeline of investigator-led and commercial trials that continues to benefit children with sight-threatening uveitis. It enabled additional academic and commercial partnerships including the MRC/Versus Arthritis-funded Stratified Medicine ‘CLUSTER’ Consortium [5.10] in which UoL are leading, along with UoB, the uveitis and industry workstreams in collaboration with five major pharmaceutical partners: AbbVie, UCB, GSK, Pfizer and Sobi. This has enabled continued close collaboration with children and their families, tackling together the challenge of determining the very best way of treating children with sight-threatening uveitis.