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

Rina La Distia Nora; Ikhwanuliman Putera; Mei Riasanti; Ratna Sitompul; Lukman Edwar; Made Susiyanti; Yulia Aziza; Muhammad Zakiy Waliyuddin; Erica Widodo; Ulifna Alfiya Sifyana; Priscilla Jessica; Rachel Ethelind; Gurmeet Singh; Willem A Dik; Saskia M Rombach; P Martin van Hagen

doi:10.1016/j.eclinm.2025.103511

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

EClinicalMedicine. 2025 Sep 17:88:103511. doi: 10.1016/j.eclinm.2025.103511. eCollection 2025 Oct.

Authors

Rina La Distia Nora^{1

2}, Ikhwanuliman Putera^{1

2

3

4}, Mei Riasanti¹, Ratna Sitompul¹, Lukman Edwar¹, Made Susiyanti¹, Yulia Aziza¹, Muhammad Zakiy Waliyuddin¹, Erica Widodo¹, Ulifna Alfiya Sifyana¹, Priscilla Jessica¹, Rachel Ethelind¹, Gurmeet Singh⁵, Willem A Dik², Saskia M Rombach⁴, P Martin van Hagen^{1

2

4

6}

Affiliations

¹ Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
² Laboratory of Medical Immunology, Department of Immunology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
³ Department of Ophthalmology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
⁴ Department of Internal Medicine, Section Allergy & Clinical Immunology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
⁵ Department of Internal Medicine, Respirology and Critical Illness Division, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
⁶ Department of Immunology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Abstract

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, p = 0.0060). Over the subsequent follow-up period, complete uveitis resolution was observed in 34 and 24 participants assigned to the ATT and the control groups, respectively. Additionally, uveitis relapse occurred in fewer participants assigned to the ATT group compared to those assigned to the control group (2/34 participants, 5.9% vs. 7/24 participants, 29.2%; HR 0.20, 95% CI 0.05-0.89, p = 0.0210). The findings regarding uveitis resolution and relapse rates were consistent in the per-protocol analysis.

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).

Keywords: Antitubercular therapy; Corticosteroids; Interferon-gamma release assay; Steroid; Tuberculosis; Uveitis.

Associated data

ClinicalTrials.gov/NCT05005637