Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis
Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis
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DOI：
10.1183/13993003.00724-2015
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发表时间：
2016-02-01
影响因子：
24.3
通讯作者：
Dannemann, Brian
中科院分区：
文献类型：
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作者：
Pym, Alexander S.;Diacon, Andreas H.;Dannemann, Brian
在之前的安慰剂对照 2 期试验（TMC207-C208；NCT00449644）中，将贝达喹啉（一种二芳基喹啉）添加到耐多药结核病 (MDR-TB) 治疗方案中可提高治愈率。本文报道的当前 2 期、多中心、开放标签、单臂试验（TMC207-C209；NCT00910871）旨在确认贝达喹啉的安全性和有效性。新诊断或既往治疗的耐多药结核病患者（包括广泛耐药前 (pre-XDR)-TB 或广泛耐药 (XDR)-TB）接受贝达喹啉治疗 24 周，并以抗结核药物为背景方案继续按照国家结核病规划治疗指南进行。在开始使用贝达喹啉期间和之后 120 周内对患者进行评估。 在 233 名入组患者中，63.5% 患有耐多药结核病，18.9% 患有前广泛耐药结核病，16.3% 患有广泛耐药结核病，其中 87.1% 的患者在入组前服用过二线药物。 16 名患者（6.9%）死亡。 20 名患者 (8.6%) 在第 24 周之前停药，最常见的是由于不良事件或耐多药结核病相关事件。不良事件通常是与耐多药结核病治疗相关的不良事件。在有效人群 (n=205) 中，120 周时培养物转化（缺失结果归类为失败）为 72.2%，耐多药结核病、广泛耐药结核病前期和广泛耐药结核病患者的培养物转化率分别为 73.1%、70.5% 和 62.2%。在背景治疗方案中添加贝达喹啉具有良好的耐受性，并在这一临床相关的耐多药结核病患者队列中产生了良好的结果。
Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB.