Adalimumab is already used in the NHS for arthritis and some forms of eye inflammation. It’s the only non-steroid treatment licensed for uveitis.
The ASTUTE trial recruited patients with non-infectious uveitis at 18 hospitals across the UK. Adalimumab was given alongside standard care.
Uveitis is inflammation inside the eye. Non-infectious uveitis is a leading cause of blindness in high-income countries. It is considered rare but is mostly seen in people of working age.
The trial was led by Bristol and Oxford Universities and run from the Bristol Trials Centre, with Bristol Eye Hospital, run by BFT, a major recruiting centre. It was also supported by Birdshot Uveitis Society and the National Institute for Health and Care Research (NIHR) Biomedical Research Centres at Moorfields and Oxford.
Everyone in the trial was given adalimumab for 16 weeks at first. Those whose eyes settled then continued either on the drug or on a dummy injection, with neither the patients nor their doctors knowing which. A year later, 31.4% of those still on adalimumab had experienced a relapse or needed more treatment, compared with 59% of those on the dummy injection.
The National Institute for Health and Care Excellence (NICE) provide evidence-based guidelines for the NHS on treatments and care. NICE currently only funds adalimumab for non-infectious uveitis for patients who meet a narrow set of conditions, set out in guidance published in 2017 before trials in this group had been done. Around 85% of the patients randomised in ASTUTE would not have met those conditions. The benefit in this group was the same for all patients in the trial.
Dr Srilakshmi Sharma, Consultant Medical Ophthalmologist at the Oxford Eye Hospital and the trial’s senior author, said:
“We set out to answer a question that patients have been asking us in clinic for years, which is whether this drug would help them if only they were allowed to have it. The answer is yes, for many of them.
“These are people who come to our clinics with their sight at risk, and who we currently have to tell that the funding rules do not cover them. We now have UK trial evidence, from NHS clinics and patients, that the rules are drawn in the wrong place.”
Side effects were no more common on adalimumab than on the dummy injection. Two serious adverse events occurred in the whole trial, one in each group.
Chief investigator for ASTUTE Professor Andrew Dick, University of Bristol and University College London, said:
“This trial was designed to be difficult to argue with. We treated everyone first, so we knew who responded, and only then did we randomise. That design let us show, cleanly, that stopping the drug in people who are doing well on it leads to relapse in most of them. The implication for practice is straightforward: when it works, it needs to be continued, and in many more patients than are currently eligible.”
Patients helped design the trial before it opened, advising on what the study should measure and what could reasonably be asked of participants.
Annie Folkard, co-founder of the Birdshot Uveitis Society, which supported the trial, said:
“Living with uveitis means living with the fear that your sight will go. Patients helped shape this study from the start, and more than a hundred people gave up years of appointments and tests to see it through. They deserve to know that it has produced an answer that could change who gets treated.”
The researchers have already put the eligibility findings to NICE.
The ASTUTE trial was funded by the NIHR Health Technology Assessment Programme.
Paper
Adalimumab versus placebo as add-on to standard therapy for non-infectious uveitis in the United Kingdom: the ASTUTE randomised controlled trial with treatment run-in
Andrew Dick et al, published in eClinical Medicine, part of The Lancet Discovery Science