Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety

Infectious Diseases of Poverty

Fei Teng¹  Li-Li Cheng¹  Li-Jie Zhang²  Yu-Xian Sun²  Wei Shu²  Shi-Heng Xie²  Yu-Hong Liu²  Jing-Tao Gao²  Yu-Jia Ning²  Hua Wang³  Meng-Qiu Gao⁴  Li Xie⁴  Yi Pei⁵  Gui-Hui Wu⁶  Wen-Long Guan⁷  Xiao-Feng Yan⁸  Xiao-Hong Chen⁹  Xin-Jie Li^1,10  Cui Cai^1,11  Qing-Shan Cai^1,12  Shu-Jun Geng^1,13  Long Jin^1,14  Pei-Lan Zong^1,15  Ming-Wu Li^1,16  Jian-Yun Wang^1,17  Tong-Xia Li^1,18  Yu Xiong^1,19  Lin Fan^2,20  Qian-Hong Wu^2,21  Wei Chen^2,22  Pei-Jun Tang^2,23  Lin Xu^2,24  Ma Zhuo^2,25  Yan-Fang Miao^2,26  Yun Zhou^2,27  Yi Zeng^2,28  Yu Chen^2,29  Guo-Bao Li^3,30  Da-Peng Bai^3,31  Guo-Li Yang^3,32  Ji-Chan Shi^3,33  Juan Du^3,34  Leonardo Martinez^3,35 

[1] Beijing Innovation Alliance of TB Diagnosis and Treatment, Beijing, People’s Republic of China;Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, Tongzhou District, 101149, Beijing, People’s Republic of China;Department of Tuberculosis, Anhui Chest Hospital, Hefei, People’s Republic of China;Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China;Department of Tuberculosis, Changsha Central Hospital, Changsha, People’s Republic of China;Department of Tuberculosis, Chengdu Public Health Clinical Center, Chengdu, People’s Republic of China;Department of Tuberculosis, Chest Hospital of Xinjiang Uyghur Autonomous Region of the PRC, Urumchi, People’s Republic of China;Department of Tuberculosis, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China;Department of Tuberculosis, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, People’s Republic of China;Department of Tuberculosis, Guangzhou Chest Hospital, Guangzhou, People’s Republic of China;Department of Tuberculosis, Guiyang Public Health Clinical Center, Guiyang, People’s Republic of China;Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China;Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, People’s Republic of China;Department of Tuberculosis, Infectious Diseases Hospital Heilongjiang Province, Harbin, People’s Republic of China;Department of Tuberculosis, Jiangxi Chest (Third People) Hospital, Nanchang, People’s Republic of China;Department of Tuberculosis, Kunming Third People’s Hospital, Kunming, People’s Republic of China;Department of Tuberculosis, Lanzhou Pulmonary Hospital, Lanzhou, People’s Republic of China;Department of Tuberculosis, Qingdao Chest Hospital, Qingdao, People’s Republic of China;Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan, People’s Republic of China;Department of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai, People’s Republic of China;Department of Tuberculosis, Shanxi Provincial Tuberculosis Institute, Xi’an, People’s Republic of China;Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, People’s Republic of China;Department of Tuberculosis, The Fifth People’s Hospital of Suzhou, Infectious Disease Hospital, Affiliated to Soochow University, Suzhou, People’s Republic of China;Department of Tuberculosis, The Fourth People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China;Department of Tuberculosis, The Fourth People’s Hospital of QingHai Province, Xining, People’s Republic of China;Department of Tuberculosis, The Fourth People’s Hospital of Taiyuan, Taiyuan, People’s Republic of China;Department of Tuberculosis, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China;Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, People’s Republic of China;Department of Tuberculosis, The Sixth People’s Hospital of Zhengzhou, Zhengzhou, People’s Republic of China;Department of Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China;Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People’s Republic of China;Department of Tuberculosis, Tuberculosis Hospital of Jilin Province, Changchun, People’s Republic of China;Department of Tuberculosis, Wenzhou Central Hospital, Wenzhou, People’s Republic of China;Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, People’s Republic of China;Division of Infectious Diseases and Geographic Medicine, School of Medicine, Stanford University, Palo Alto, CA, USA;

关键词: Tuberculosis;    Multidrug-resistant;    Bedaquiline;    Safety;    Surveillance program;    China;   

DOI  :  10.1186/s40249-021-00819-2

来源: Springer

【 摘 要 】

BackgroundWorld 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).MethodsAEs 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.ResultsBy 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.ConclusionsBedaquiline 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.

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