Zhurkin Dzmitriy, Gurbanova Elmira, Campbell Jonathon R, Menzies Dick, Setkina Svetlana, Hurevich Hennadz, Solodovnikova Varvara, Viatushka Dzmitry, Altraja Alan, Skrahina Alena
Republican Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk, Belarus.
Lung Clinic, University of Tartu, Tartu, Estonia.
ERJ Open Res. 2022 May 16;8(2). doi: 10.1183/23120541.00685-2021. eCollection 2022 Apr.
Bedaquiline is now considered a first-line medicine for treatment of rifampicin-resistant tuberculosis (RR-TB). We evaluated the safety of treatment with bedaquiline for longer than 190 days in individuals with RR-TB under programmatic conditions. In a prospective cohort study enrolling pulmonary RR-TB patients, we initiated bedaquiline-based treatment at a tertiary hospital in Belarus. We defined standard bedaquiline use as <190 days and prolonged as ≥190 days. We recorded adverse events (AEs) and classified their seriousness and relation to bedaquiline. Our primary outcome in regression analyses was the incidence of serious AEs occurring within 5 months of bedaquiline cessation. We used generalised estimating equations to estimate the adjusted incidence rate ratio (aIRR) of serious AEs between the prolonged and standard bedaquiline groups. We enrolled 113 patients, 83 (73%) of whom received standard and 30 (27%) received prolonged treatment. A total of 2030 AEs occurred during treatment. Of these, 63 (3.1%) were serious AEs occurring within 5 months of bedaquiline cessation; QTcF prolongation was the most common bedaquiline-related serious AE. The incidence of serious AEs per 100 person-months was 5.4 (3.9 to 7.2) in the standard group and 4.4 (2.6 to 7.0) in the prolonged group. In adjusted analyses, serious AEs were no different (aIRR: 0.82, 95% CI 0.42-1.61) in the prolonged group. One patient in the standard bedaquiline group died of acute cardiopulmonary failure deemed possibly related to bedaquiline. Prolonged use of bedaquiline under programmatic conditions appears safe. Clinicians should carefully monitor QTcF interval since its prolongation was commonly observed.
贝达喹啉现已被视为治疗耐利福平结核病（RR-TB）的一线药物。我们评估了在项目条件下，RR-TB患者使用贝达喹啉治疗超过190天的安全性。在一项纳入肺结核RR-TB患者的前瞻性队列研究中，我们在白俄罗斯的一家三级医院启动了以贝达喹啉为基础的治疗。我们将标准贝达喹啉使用定义为<190天，延长使用定义为≥190天。我们记录不良事件（AE），并对其严重程度及与贝达喹啉的关系进行分类。回归分析中的主要结局是贝达喹啉停药后5个月内发生严重AE的发生率。我们使用广义估计方程来估计延长使用组与标准使用组之间严重AE的调整发病率比（aIRR）。我们纳入了113例患者，其中83例（73%）接受标准治疗，30例（27%）接受延长治疗。治疗期间共发生2030次AE。其中，63次（3.1%）是贝达喹啉停药后5个月内发生的严重AE；QTcF延长是最常见的与贝达喹啉相关的严重AE。标准组每100人月严重AE的发生率为5.4（3.9至7.2），延长组为4.4（2.6至7.0）。在调整分析中，延长使用组的严重AE无差异（aIRR：0.82，95%CI 0.42-1.61）。标准贝达喹啉组有1例患者死于急性心肺功能衰竭，认为可能与贝达喹啉有关。在项目条件下延长使用贝达喹啉似乎是安全的。由于常见QTcF延长，临床医生应仔细监测QTcF间期。
