Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, Tongzhou District, Beijing, 101149, People's Republic of China.
Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, People's Republic of China.
Infect Dis Poverty. 2021 Mar 19;10(1):32. doi: 10.1186/s40249-021-00819-2.
World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP).
AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort.
By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually.
Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.
世界卫生组织建议各国为耐多药/广泛耐药结核病（DR-TB）引入新药和短程治疗方案，应开发和实施主动药物警戒系统，以检测、报告和管理不良事件。本研究旨在通过新药引进和保护计划（NDIP）的主动药物安全监测（aDSM）系统，评估贝达喹啉方案在中国多药耐药（MDR）/广泛耐药（XDR）-TB 患者队列中不良事件（AE）的频率和严重程度。
2018 年 2 月至 2019 年 12 月期间，在中国 54 个地点，从患者入组开始至治疗期间，前瞻性收集人口统计学、细菌学、影像学和临床数据，以监测贝达喹啉治疗的不良事件。这是一项中期分析，包括仍在接受治疗和已完成治疗的患者。对队列中评估的患者进行描述性分析。
截至 2019 年 12 月 31 日，共有 1162 名患者接受了含贝达喹啉的抗结核治疗。总体而言，共报告了 1563 例不良事件，其中 66.9%为轻度（1-2 级），33.1%为严重（3-5 级）。贝达喹啉治疗的中位持续时间为 167.0[四分位距（IQR）：75-169]天。86（7.4%）例患者接受了 36 周的贝达喹啉延长治疗。不良事件和严重不良事件的发生率分别为 47.1%和 7.8%。最常报告的不良事件是 QT 间期延长（24.7%）和肝毒性（16.4%）。有 14 例（1.2%）不良事件导致死亡。在有 Fridericia 公式（QTcF）校正 QT 间期可用数据的患者中，3.1%（32/1044）出现基线后 QTcF≥500ms，15.7%（132/839）至少有一次 QTcF 从基线变化≥60ms。49（4.2%）例患者因 QT 延长不良事件而停止使用贝达喹啉。190 例患者报告了 361 例肝毒性不良事件，肝毒性不良事件的发生率排名第二，且发生率较高。34 例患者报告了 43 例与贝达喹啉相关的肝损伤不良事件，远低于与丙硫异烟胺、吡嗪酰胺和对氨基水杨酸的不良事件。
在本临床患者人群中，贝达喹啉总体耐受性良好，安全性问题较少，未发现新的安全性信号。死亡率通常较低。这些数据提供了重要的积极影响，支持世界卫生组织最近广泛使用贝达喹啉的建议。
