ASTUTE

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness. The ASTUTE pragmatic randomized controlled trial 

Summary

Autoimmune 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. Two in 10,000 people are at risk of serious sight loss from uveitis. Usual treatment for autoimmune uveitis involves low dose steroids and one or two other drugs to reduce inflammation. Unfortunately, many patients do not respond to or tolerate usual treatment, or 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. Adalimumab is an expensive new drug that targets chemicals released by inflamed tissue, neutralizing their damage to the body.

Two recent studies suggest fortnightly adalimumab is, on average, 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.

This study 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 trial period, if necessary in combination with low dose of steroids; these 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.

Then, patients who are successfully treated with adalimumab and low dose steroids will enter the main study. They will be given adalimumab or a dummy treatment, in combination with their other medications (including low dose steroids). Chance will determine who receives which treatment and neither patients nor their eye doctors will know. Regular eye examinations, tests and questionnaires will be used to assess how well patients are doing. This part of the study, which will treat and follow up patients for 12 to 36 months, will find out whether adalimumab is better at preventing recurrence of uveitis than the dummy treatment and whether adalimumab is cost -effective compared to the dummy treatment.

Patients with uveitis have contributed to the study from the start, helping to: design the protocol to ensure it applies to uveitis patients who may benefit; developing and testing a 'quality of life' questionnaire about the side effects of medications, impact on work and mood; co-authoring the lay summary; helping to draft the application, providing feedback on the trial design and participating in a national survey to assess support for the study. They will continue to contribute in these ways and provide support to patients, if funding is awarded. The research team includes eye doctors and researchers with expertise in doing eye studies. A registered clinical trials unit, ophthalmology research networks and patient groups will collaborate to conduct the study. The results will be disseminated through NHS England, patient societies and through medical journals.

Further Information

https://bristoltrialscentre.blogs.bristol.ac.uk/details-of-studies/astute/