Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study
Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study
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DOI：
10.1016/s2213-2600(18)30235-2
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发表时间：
2018-09-01
影响因子：
76.2
通讯作者：
Conradie, Francesca
中科院分区：
文献类型：
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作者：
Schnippel, Kathryn;Ndjeka, Norbert;Conradie, Francesca
背景在一项2b期临床试验中，在耐多药结核病的治疗中加入贝达喹啉与死亡风险增加有关，因此世卫组织对此持谨慎态度。在同情获取计划和当地监管机构批准后，南非国家结核病规划署于2015年3月开始广泛使用贝达喹啉，特别是在没有其他有效治疗选择的广泛耐药结核病患者中。我们的目的是比较患者的标准方案，包括bedaquiline.Methods方案的患者的死亡率，在这项回顾性队列研究中，我们分析了患者的数据，从南非利福平耐药结核病病例登记（EDRweb），并确定额外的死亡率使用国家生命统计登记。我们排除了在2014年7月1日之前或2016年3月31日之后开始治疗的患者;年龄小于15岁或年龄大于75岁的患者;没有记录的利福平耐药患者，以及患有前广泛耐药结核病（对二线注射剂或氟喹诺酮进一步耐药的多重耐药结核病）的患者。我们比较了在治疗方案中接受贝达喹啉和未接受贝达喹啉的患者的全因死亡率。未接受贝达喹啉治疗的患者在其治疗方案中使用卡那霉素或卷曲霉素和阿托沙星作为核心药物。我们分别估计了耐多药或耐利福平结核病和广泛耐药结核病的死亡风险比，并使用倾向评分五分位数分层进行了性别、年龄、HIV和抗逆转录病毒治疗状态、既往结核病史、有效身份证号、结果2014年7月1日至2016年3月31日期间，EDRweb上登记了24014例结核病病例。其中，19，617例患者开始治疗并符合我们的分析资格标准。对18542例多重耐药或利福平耐药结核病患者中的743例（4.0%）和1075例广泛耐药结核病患者中的273例（25.4%）给予含贝达喹啉的方案。在1016例接受贝达喹啉治疗的患者中，报告了128例死亡（12.6%），在18601例接受标准方案治疗的患者中，报告了4612例死亡（24.8%）。贝达喹啉与耐多药或耐利福平结核病患者的全因死亡风险降低相关（风险比[HR] 0.35，95% CI 0.28-0.46）和广泛耐药结核病（0.26，0.18-0.38）解释我们的回顾性队列分析的常规报告的数据在高艾滋病毒和广泛的背景下，耐药结核病患病率显示，以贝达喹啉为基础的治疗方案与大幅减少有关版权所有（C）2018爱思唯尔有限公司保留所有权利。
Background Addition of bedaquiline to treatment for multidrug-resistant tuberculosis was associated with an increased risk of death in a phase 2b clinical trial, resulting in caution from WHO. Following a compassionate access programme and local regulatory approval, the South African National Tuberculosis Programme began widespread use of bedaquiline in March, 2015, especially among patients with extensively drug resistant tuberculosis for whom no other effective treatment options were available. We aimed to compare mortality in patients on standard regimens with that of patients on regimens including bedaquiline.Methods In this retrospective cohort study, we analysed patient data from the South African rifampicin-resistant tuberculosis case register (EDRweb), and identified additional mortality using the national vital statistics register. We excluded patients who started treatment before July 1, 2014, or after March 31, 2016; patients younger than 15 years or older than 75 years; patients without documented rifampicin resistance, and patients with pre-extensively drugresistant tuberculosis (multidrug-resistant tuberculosis with further resistance to a second-line injectable or fluoroquinolone). We compared all-cause mortality between patients who received bedaquiline in treatment regimens and those who did not. Patients who did not receive bedaquiline had kanamycin or capreomycin and moxifloxacin as core medicines in their regimen. We estimated hazard ratios for mortality separately for multidrug-resistant or rifampicin-resistant tuberculosis and extensively drug-resistant tuberculosis and adjusted using propensity score quintile strata for the potential confounders of sex, age, HIV and antiretroviral therapy status, history of prior tuberculosis, valid identification number, and year and province of treatment.Findings 24 014 tuberculosis cases were registered in the EDRweb between July 1, 2014, and March 31, 2016. Of these, 19 617 patients initiated treatment and met our analysis eligibility criteria. A bedaquiline-containing regimen was given to 743 (4.0%) of 18 542 patients with multidrug-resistant or rifampicin-resistant tuberculosis and 273 (25.4%) of 1075 patients with extensively drug-resistant tuberculosis. Among 1016 patients who received bedaquiline, 128 deaths (12.6%) were reported, and there were 4612 deaths (24.8%) among 18 601 patients on the standard regimens. Bedaquiline was associated with a reduction in the risk of all-cause mortality for patients with multidrug-resistant or rifampicin-resistant tuberculosis (hazard ratio [HR] 0.35, 95% CI 0.28-0.46) and extensively drugresistant tuberculosis (0.26, 0.18-0.38) compared with standard regimens.Interpretation Our retrospective cohort analysis of routinely reported data in the context of high HIV and extensively drug-resistant tuberculosis prevalence showed that bedaquiline-based treatment regimens were associated with a large reduction Copyright (C) 2018 Elsevier Ltd. All rights reserved.