Two in 10,000 people are at risk of serious sight loss from a form of eye inflammation known as uveitis. A new clinical research study, led by the University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust (UHBW), will evaluate a drug combination treatment for the eye disease thanks to funding of £2.5 million by the National Institute for Health Research (NIHR). The study will be co-ordinated by the University’s Bristol Trials Centre (CTEU).
Three recent studies suggest fortnightly adalimumab is an effective way to treat uveitis in some patients. However, drugs like adalimumab can have serious side effects and more evidence is required to identify which patients with uveitis benefit the most from adalimumab, both with respect to their vision and quality of life, including treatment side effects.
The ASTUTE trial aims, first, to identify patients who are most likely to benefit from adalimumab. All eligible patients who consent will be given adalimumab for a 16-week test period, if necessary, in combination with low dose of steroids. Patients will include those with impaired vision due to uveitis, requiring high-dose steroids to bring the disease under control, and those with better vision but who require high-dose steroids to keep the uveitis under control. Over the 16 weeks, doctors will aim to reduce the steroid dose to a low level that should not cause side effects longer term.
Then, patients who are successfully treated with adalimumab and low-dose steroids (inactive disease at the end of 16-weeks) will enter the main study. They will be assigned by chance to receive adalimumab or a placebo treatment, in combination with their other medications (including low-dose steroids). In this randomised study, neither patients nor their eye doctors will know what treatment a patient is receiving.
Regular eye examinations, tests and questionnaires will be used to assess how well patients are doing. In this part of the study, patients will be treated and followed up for 12 to 30 months to find out whether adalimumab is better at preventing recurrence of uveitis than the placebo treatment and whether adalimumab is cost-effective compared to the placebo treatment.
Patients on the placebo-controlled randomised trial will be recruited from more than 20 UK NHS hospitals. Four hundred patients will be allocated to the 16-week test period, of which 174 will progress into the main randomised study.
Andrew Dick, Professor of Ophthalmology from the Bristol Medical School: Translational Health Sciences (THS) and chief investigator for the trial, said: “Usual treatment for autoimmune uveitis involves steroids and one or two other drugs to reduce inflammation. Unfortunately, there remain patients who do not respond to or tolerate usual treatment, or they still need high-dose steroids to control the uveitis. Long-term high-dose steroids increase the risk of heart attack, stroke, and infection and affect physical and mental health.
“Recent studies suggest a drug called adalimumab, which neutralises a chemical in the body called TNF-alpha, is an effective way to treat uveitis in some patients. Our study hopes to provide clearer evidence to identify which patients with uveitis benefit the most from adalimumab, both with respect to their vision and quality of life, including treatment side effects.”
Srilakshmi Sharma, Consultant in Ophthalmology from Oxford Eye Hospital and Oxford University and deputy chief investigator and national clinical co-lead for the study, added: “Part of this study is aiming to understand who benefits most from a medication, something which has not been systematically studied in other uveitis trials. By working with uveitis specialists throughout the country we wish to make sure that as many patients as possible have the opportunity to participate in this trial.”
Autoimmune uveitis (“uveitis”) is a term for several rare eye diseases in which the body’s own immune system causes sight-threatening damage to the light sensitive retina at the back of the eye. Uveitis causes sight loss from inflammation inside the eye, damage to blood vessels in the retina or leakage of fluid into the central, most sensitive area of the retina.
Patients with uveitis have contributed to this study from the start, helping to: design the protocol; identify patient-reported outcome measures; co-author the lay summary; draft the funding application; provide feedback on the trial design and participating in a national survey to assess support for the study.
This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (project reference 16/24/09).