Khan Uzma, Rich Michael, Franke Molly F, Lachenal Nathalie, Ahmed Saman, Bekele Amsalu, Isani Afshan K, Hewison Catherine, Sari Cut Yulia Indah, Tan Cecilio L, Varaine Francis, Flores Edwin Herrera, Putri Fauziah Asnely, Faqirzai Jamil, Beauchamp Jude, Vo Luan Nguyen Quang, Siddiqui Muhammad Rafi, Seung Kwonjune, Bastard Mathieu, Nkunkanyirazo Patrick, Kiria Nana, Khan Munira, Algozhin Yerkebulan, Melikyan Nara, Saki Nazis Arefin, Vilbrun Stalz C, Fatima Razia, Naing Ye Yint, Islam Shirajul, Mamsa Shahid, Mitnick Carole D, Huerga Helena, Khan Palwasha Y
Interactive Research & Development (IRD) Global, Singapore, Singapore.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
Clin Infect Dis. 2025 Aug 1;81(1):153-158. doi: 10.1093/cid/ciae601.
The 2022 World Health Organization (WHO) guidelines on multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) recommend 6 months of bedaquiline (Bdq) in the all-oral 9-month shorter regimen and 6 months or longer for Bdq and delamanid (Dlm) in the 18-20-month longer regimen. However, lack of evidence on extended treatment using Bdq or Dlm has limited their use to 6 months. We examine the frequency and incidence of QT prolongation based on duration of Bdq and/or Dlm use in longer regimens.
We analyzed a prospective cohort of MDR/RR-TB patients from 16 countries who initiated treatment with Bdq and/or Dlm containing regimens from 1 April 2015 to 30 September 2018. Data were systematically collected using a shared protocol. The outcome of interest was the first clinically relevant prolonged QT interval (grade 3 or above) or a serious adverse event (SAE) involving prolonged QT of any grade.
Among 2553 patients, 59% received >6 months of Bdq and/or Dlm. Of these, 579 (20.9%) patients experienced a prolonged QT event, the majority (95.5%) being grade 1 or 2. Sixty-four (2.5%) patients experienced the outcome of interest with only 12 (0.5%) having ≥1 QT prolonging drugs permanently suspended. The incidence rate of the first prolonged QT event was highest in the first six months of treatment and lower in subsequent 6-month periods.
We demonstrate that Bdq and/or Dlm use beyond 6 months is safe in longer MDR/RR-TB regimens with most clinically relevant QT prolongation events occurring in the first 6 months. Electrocardiogram (ECG) monitoring for early identification of QT prolongating events is possible in programmatic conditions.
世界卫生组织（WHO）2022年耐多药/利福平耐药结核病（MDR/RR-TB）指南推荐，在全口服9个月的短程治疗方案中使用6个月的贝达喹啉（Bdq），在18至20个月的长程治疗方案中使用6个月或更长时间的Bdq和地拉曼丁（Dlm）。然而，由于缺乏关于延长使用Bdq或Dlm治疗的证据，它们的使用期限被限制在6个月。我们根据在长程治疗方案中使用Bdq和/或Dlm的持续时间，研究QT间期延长的频率和发生率。
我们分析了来自16个国家的MDR/RR-TB患者的前瞻性队列，这些患者于2015年4月1日至2018年9月30日开始使用含Bdq和/或Dlm的治疗方案。数据通过共享方案进行系统收集。感兴趣的结局是首次出现临床相关的QT间期延长（3级或以上）或任何级别的涉及QT延长的严重不良事件（SAE）。
在2553例患者中，59%接受了超过6个月的Bdq和/或Dlm治疗。其中，579例（20.9%）患者发生了QT间期延长事件，大多数（95.5%）为1级或2级。64例（2.5%）患者出现了感兴趣的结局，只有12例（0.5%）患者永久停用了≥1种延长QT的药物。首次QT间期延长事件的发生率在治疗的前6个月最高，在随后的6个月期间较低。
我们证明，在更长的MDR/RR-TB治疗方案中，使用超过6个月的Bdq和/或Dlm是安全的，大多数临床相关的QT间期延长事件发生在治疗的前6个月。在项目实施条件下，可以进行心电图（ECG）监测以早期识别QT间期延长事件。
