Abstract / Summary
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. Findings: 182 participants completed the TRI, 119 (65.4%) responded, and 115 were randomised (60 adalimumab, 55 placebo). At 12 months, 31.4% (adalimumab) and 59.0% (placebo) had experienced TF (hazard ratio 0.42, 95% CI 0.23–0.75, p = 0.003). Among patients ineligible for NHS treatment (85%), the effect was similar (hazard ratio 0.37, 95% CI 0.20–0.71, p = 0.003). Adverse events were similarly frequent; two were serious, one per group. Incremental cost was £2320 per TF avoided. Interpretation: Adalimumab added to standard care reduces treatment failure in NIU, including in patients with macular oedema, unilateral disease, and steroid-dependent inactive uveitis, and is affordable. Future work should identify complementary treatments for disease refractory to adalimumab. Funding: Health Technology Assessment Programme, National Institute for Health and Care Research (NIHR); Biogen International GmbH (Baar, Switzerland) provided the placebo for the trial.