Medical Research Council-funded scientists are beginning a five-year study of childhood arthritis and its linked eye inflammation called uveitis, with the aim of better understanding how to treat the complex condition, which affects one in 1,000 under 16 year olds in the UK.
With nearly £5 million in funding (including £0.5m from Arthritis Research UK), the CLUSTER childhood arthritis study will team scientists at the UCL Great Ormond Street Institute of Child Health (ICH) and other UK institutions* to follow the health trajectories of 5,000 children with the condition.
The initiative is one of four ‘stratified medicine’ projects being funded by the MRC, which is investing £15 million in studies that will establish ground-breaking approaches in treating prostate cancer, kidney disease, alcoholic hepatitis and childhood arthritis. Stratified medicine, also referred to as personalised medicine or precision medicine, is an emerging approach for disease diagnosis and treatment that considers patients’ genes, environment and lifestyle to create tailored therapies instead of a one-size-fits-all approach.
Childhood arthritis can cause long-term disability and poor quality of life – sometimes well into adulthood. If it isn’t diagnosed and treated early, patients may require hip and knee replacements, are significantly shorter than their peers, and some end up in wheelchairs. For those patients who also have uveitis, a condition where the inside of the eyes become inflamed, there is also a significant risk of vision loss and blindness.
Currently, young people diagnosed with arthritis in the UK are given a single drug therapy, but it only works in about 50% of cases. The remaining half must try other treatments, one after the other, to find a therapy which works for them. Along the way, they may experience painful side effects, time out of school and even a worsening of their symptoms.
Ultimately, the researchers in the trial hope to identify a simple biomarker test that will:
- Pave the way to new treatment options, identifying potential new therapies and eventually the trialling of new drugs which work better with fewer side effects
- Help doctors define the right medication for the right duration for each individual patient on the first try. Identifying the right treatment ensures symptoms are managed and that the condition doesn’t develop into lifelong disability
- Identify which children are at risk of uveitis, a serious eye-inflammation which affects 15% those with childhood arthritis. Currently, patients visit eye specialists every three to six months to screen for this secondary condition
- Project long-term outcomes for these children – scientists will track patient health over decades, so they can better predict what may be ahead for these children
Lead researcher, Professor Lucy Wedderburn at the UCL ICH and Great Ormond Street Hospital, said: “Using a stratified medicine approach could be a gamechanger in childhood arthritis and its associated uveitis. A biomarker test could lead to methods for accurately predicting the right treatment for the right duration, halting the worsening of symptoms and leading to shorter time to remission. Nothing like that has been done before in this area of research.”
Eilean MacDonald, an 18-year-old patient, who was diagnosed with childhood arthritis as an 18-month-old baby, is taking part in the study. It took years of trying various medications until she found the right treatment to alleviate her symptoms. She’s now on crutches and requires an ankle replacement this summer.
MacDonald said: “When you think of arthritis you see a 70-year-old lady with stiff hands, not an 18-month-old baby or a teenager. People don’t believe children can get arthritis but we do. I’ve missed school and had to quit activities I loved because of my condition.
“This research is so important – it could mean the next generation of kids with childhood arthritis won’t have to go through what I did. They could have the right therapy handpicked for them, reducing the impact it has on their lives. They could have even one piece of their life that’s more consistent and predictable while living with this disease.”
Professor Sir John Savill, Chief Executive Officer at the MRC, said: “Stratified medicine is reshaping the medical landscape by taking a patient-first approach that looks at how – and why – different groups of patients respond differently to therapies. Instead of looking for a ‘one-size-fits-all’ solution, stratified medicine is increasing what we know about diseases and how they affect individuals, and applying these findings to current tools in diagnostics and treatment to improve health outcomes. I am particularly pleased to see the potential benefits of this research approach extended to children with a life-changing condition.”
More information about the CLUSTER Consortium
Researchers from UCL, and partners including Dr Chris Wallace from the MRC Biostatistics Unit, have come together to drive a UK-wide effort to drive the development of new, targeted treatments for children and young people with juvenile idiopathic arthritis (JIA) and its associated eye-inflammation condition, uveitis.
The CLUSTER consortium has been awarded £5 million from the UK’s Medical Research Council (MRC) with partnership funding from Arthritis Research UK. It brings together world-leading clinical, academic, scientific, statistical and industry expertise in childhood arthritis and its associated eye inflammation uveitis, in partnership with children, young people and their families. Its aim is to improve the lives of children living with these life-changing, complex conditions. Starting in July 2018, CLUSTER will help clinicians to target specific treatments for patients.
JIA affects around one in 1000 children and young people and can cause long-term disability, significantly impacting on those affected well into adult life. Up to 15 per cent of children with JIA have uveitis which may cause visual impairment; children and young people can become certified legally blind. This five year project will systematically analyse data that is captured from national studies and trials of patients with JIA and JIA-uveitis. It will look for gene alterations, immune cell differences, blood proteins and clinical features that are typical of patients who respond to therapies well, and in patients who develop uveitis. Ultimately, the researchers hope to identify a panel of tests that doctors can use to help make sure treatments are targeted specifically to groups of patients with similar characteristics. The work will also help influence, design and monitor future clinical trials allowing researchers to better understand the condition and test advanced treatments for these debilitating conditions.
The research will build on the previous MRC supported-CHART study, which brought together data on 5000 patients with JIA and key collaborative partners from across the UK and beyond. The CLUSTER consortium is supported through the MRC’s stratified medicine programme and will be co-funded through a partnership between MRC and Arthritis Research UK. As an integral part of the Consortium’s work, CLUSTER will also receive co-funding from GOSH Children’s Charity and Olivia’s Vision.
The ten CLUSTER co-investigators [Professor Lucy Wedderburn (UCL and GOSH), Professor Wendy Thomson (University of Manchester), Professor Andrew Dick (UCL), Prof. Kimme Hyrich (University of Manchester), Dr Nophar Geifman (University of Manchester), Professor Souyma Raychaudhuri (University of Manchester), Professor Michael Beresford (University of Liverpool and Alder Hey Children’s NHS Foundation Trust), Professor. A.V. Ramanan (University Hospitals Bristol NHS Foundation Trust), Dr Chris Wallace (MRC Biostatistics Unit, University of Cambridge) and Dr Michael Barnes (Queen Mary’s University of London)] have made renowned research contributions in the fields of stratified medicine for childhood arthritis and uveitis.
Also reported on MRC website: https://www.mrc.ac.uk/news/browse/study-of-over-5-000-young-people-to-personalise-treatment-for-childhood-arthritis/