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

Summary: Background: Immune-mediated non-infectious uveitis (NIU) is a leading cause of blindness in high-income countries. Adalimumab is the only licensed non-corticosteroid drug for non-infectious intermediate, posterior or panuveitis. We evaluated the efficacy, safety and cost-effectiveness of an adalimumab biosimilar as add-on therapy for a broad NIU population.

Methods

This multicentre, placebo-controlled randomised trial recruited adults with sight-threatening or controlled NIU requiring oral prednisolone >5 mg/day from 18 UK NHS ophthalmology departments between 29 July 2021 and 7 June 2024. After a 16-week treatment run-in (TRI) with adalimumab, responders (prednisolone ≤5 mg/day, no active disease) were randomised 1:1 (parallel groups; concealed web-based allocation) to fortnightly subcutaneous 40 mg adalimumab (biosimilar) or placebo as add-on therapy; all but the trial statistician were masked. The primary outcome, time to treatment failure (TF; disease activity or prednisolone >5 mg/day), was analysed at 12 months by intention to treat. The health economic evaluation was pre-specified in the trial protocol; we estimated incremental cost per TF avoided, NHS perspective. Registered: ISRCTN31474800.