Every year, thousands of children with juvenile idiopathic arthritis (JIA) and its associated eye inflammation (JIA-uveitis) cycle through multiple drugs that may not work, leaving them with uncontrolled inflammation, disability, and vision loss. The problem is that current classification of JIA does not tell doctors which drug to choose for which child, and there are no reliable tools to predict disease course or treatment response. This consortium aims to define “endotypes”—subgroups based on underlying disease mechanisms—and link them to biomarkers measurable in children, so that the right medicine can be given at the right time. If successful, this would allow doctors to achieve early remission, reduce side effects, and prevent lifelong disability and blindness. Children could return to school, sports, and family life sooner. The work also aims to identify predictors of which children with JIA will develop uveitis, improving screening to prevent vision loss. By integrating clinical, genetic, and immune data from a large UK cohort, the consortium will speed up the introduction of stratified medicine for childhood arthritis, reducing long-term costs to the health service and society.
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Childhood arthritis, classified under the umbrella term juvenile idiopathic arthritis, JIA, and its associated eye inflammation, JIA-uveitis, can be devastating for both child and family, and impose significant long-term economic burden on society. Despite improvements in the management of JIA, and increasing availability of new medicines, many children still undergo prolonged treatment with multiple drugs that may not work, leaving them exposed to uncontrolled inflammation, side effects, and the damaging effects of disease, which include disability, vision loss, lower quality of life and reduced chances of employment. Early control of childhood arthritis and JIA-uveitis translates to better longterm outcomes and economic benefit. However, current JIA classification does not inform choice of drug for most children, and there are no verified clinical or biological tools with which to predict disease course, select treatment or predict response. Effective strategies allowing doctors to choose the right medicine, at the right time for each child ('stratified medicine'), would increase early remission rates, reduce suffering, improve long-term outcomes and avoid years of treatment with ineffective drugs. To start to address these unmet needs, we established a partnership between 4 large UK JIA cohort studies, the Childhood Arthritis Response to Treatment (CHART) Consortium, representing 5000 children with JIA, with clinical information, biological samples, and new data. Building on our success, and strengthened by important new cohorts and investigators, we now propose an ambitious consortium, CLUSTER, bringing together internationally recognised leaders in childhood arthritis and JIA-uveitis, with new collaborators and industry partners to deliver stratified medicine for JIA. CLUSTER will include multidisciplinary expertise in clinical, molecular, genetic, immunological, and statistical sciences, with UK leaders in paediatric rheumatology and ophthalmology, and those designing and delivering clinical trials in JIA and its associated uveitis. The overall goal of CLUSTER is to define 'endotypes' (subgroups based on underlying disease mechanism) of childhood arthritis and JIA-uveitis, which more accurately reflect likely treatment response and disease course, linked to biomarkers that are feasible to measure in children, to allow targeted treatment decisions. We will adopt a P4 (predict, prevent, personalise, participatory) approach; our key scientific aims are to: 1. Identify 'biomarkers' (clinical, genetic, protein, gene expression or immune factor) that help predict treatment response in JIA, to allow a more targeted approach to medicine choices and prevent poor long-term outcomes; 2. Identify predictors (clinical, genetic, auto-antibody) of getting uveitis for children with JIA, to improve screening protocols and prevent vision loss; 3. Using specimens from both blood and inflamed joints, undertake state of the art analysis of cells, proteins and gene expression in JIA to define mechanisms of response to treatment and different disease types, and identify new treatments; 4. Integrate and explore all CLUSTER data together to define endotypes in JIA, that predict disease type or treatment response, with associated markers that can be measured, to enable personalised treatment and facilitate patient/parent participation in treatment choices; 5. Establish collaborative agreements with Industry and international partners to ensure that high-quality bio-sample collection and stratification design are used in future trials in childhood arthritis and uveitis. Our programme of work will speed up the introduction of 'stratified' medicine for children with JIA. Earlier control of inflammation and reduced exposure to side effects will allow children to return to their education and full sporting and family life activities, prevent life long disability and blindness, and reduce costs to the health service and society as a whole.
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