Antitubercular therapy for uveitis of undetermined cause with positive interferon-gamma release assay: a single-blind, single-centre, phase 2 randomised controlled trial.

Background: No randomised controlled trial (RCT) has previously evaluated the effect of antitubercular therapy (ATT) in patients with uveitis of undetermined cause who tested positive on interferon-gamma release assays (IGRA), despite the absence of other identifiable causes of uveitis. We aimed to assess the efficacy and safety of treatment involving ATT compared to treatment without ATT in these patients, with respect to uveitis resolution and reduction in the risk of relapse. Methods: We conducted a single-blind, single-centre, phase 2 RCT at the uveitis clinic of Cipto Mangunkusumo Hospital in Jakarta, Indonesia, from August 16, 2021, to February 5, 2024. Seventy-six adults with newly diagnosed, active uveitis of undetermined cause and a positive IGRA were randomised 1:1 using block randomisation (block size 4) into two groups. Participants in the ATT group received an additional full course of ATT in addition to systemic corticosteroids. The control group received systemic corticosteroids without ATT. Investigators were masked to group assignment. The primary endpoint was the complete resolution of uveitis six months after randomisation. The trial is registered at ClinicalTrials.gov (NCT05005637). Findings: Seventy-six participants were randomly assigned to either ATT (n = 37) or control (n = 39) group. At primary end point, more participants assigned to the ATT group achieved the primary outcome of complete uveitis resolution compared to the control group (30/37, 81.1% vs. 20/39 participants; 51.3%, relative risk [RR] 1.58, 95% CI 1.12-2.23, Interpretation: In IGRA-positive patients with uveitis of undetermined cause, initial treatment with ATT resulted in a significant benefit over those not receiving ATT. Funding: This work was supported by RISPRO-LPDP (Riset Inovatif Produktif-Lembaga Pengelola Dana Pendidikan).