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
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引用次数: 0
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).
背景:尽管没有其他可识别的葡萄膜炎原因,但之前没有随机对照试验(RCT)评估抗结核治疗(ATT)对干扰素γ释放试验(IGRA)阳性的不明原因葡萄膜炎患者的效果。我们的目的是在葡萄膜炎的消退和复发风险的降低方面,评估有ATT治疗与无ATT治疗在这些患者中的疗效和安全性。方法:我们于2021年8月16日至2024年2月5日在印度尼西亚雅加达Cipto Mangunkusumo医院葡萄膜炎诊所进行了一项单盲、单中心、2期随机对照试验。76例新诊断的原因不明的活动性葡萄膜炎和IGRA阳性的成年人采用分组随机(分组大小为4),按1:1随机分为两组。ATT组的参与者除了接受全身性皮质类固醇治疗外,还接受了额外的全程ATT治疗。对照组接受全身性皮质类固醇治疗,但不接受ATT治疗。调查人员不按组分配。主要终点是随机分组后6个月葡萄膜炎的完全消退。该试验已在ClinicalTrials.gov注册(NCT05005637)。结果:76名参与者被随机分为ATT组(n = 37)和对照组(n = 39)。在主要终点,与对照组相比,更多被分配到ATT组的参与者达到了葡萄膜炎完全消退的主要结局(30/37,81.1% vs. 20/39; 51.3%,相对风险[RR] 1.58, 95% CI 1.12-2.23, p = 0.0060)。在随后的随访期间,分别在34名和24名被分配到ATT组和对照组的参与者中观察到葡萄膜炎完全消退。此外,与对照组相比,ATT组患者葡萄膜炎复发的发生率更低(2/34例,5.9% vs. 7/24例,29.2%;HR 0.20, 95% CI 0.05-0.89, p = 0.0210)。关于葡萄膜炎消退和复发率的研究结果在方案分析中是一致的。解释:在原因不明的igra阳性葡萄膜炎患者中,最初接受ATT治疗的患者比未接受ATT治疗的患者获益显著。资助:这项工作得到RISPRO-LPDP (Riset innovatif produktifi - lembaga Pengelola Dana Pendidikan)的支持。
期刊介绍:
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.