Background

Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed.

Objectives

To appraise existing evidence on efficacy and safety of pretomanid in tuberculosis.

Data Sources

Pubmed, clinicaltrials.gov. and Cochrane library.

Study eligibility criteria

Quantitative studies presenting original data on clinical efficacy or safety of pretomanid.

Participants

Patients with tuberculosis.

Interventions

Treatment with pretomanid or pretomanid-containing regimens in minimum one study group.

Methods

Two authors independently extracted data and assessed risk of bias. Data on efficacy (early bactericidal activity, bactericidal activity, end-of-treatment outcomes and acquired resistance) and safety were summarized in tables. Mean differences in efficacy outcomes between regimens across studies were calculated.

Results

Eight studies were included; four randomized controlled trials on 2-week early bactericidal activity in rifampicin-susceptible tuberculosis, three trials with randomized rifampicin-susceptible tuberculosis arms and a single rifampicin-resistant tuberculosis arm (two on 8-week bactericidal activity, one on end-of-treatment outcomes), one single-arm trial with end-of-treatment outcomes in highly resistant tuberculosis. Activity of pretomanid–moxifloxacin–pyrazinamide was superior to standard treatment on daily change in colony-forming units at days 0–2, 0–56 and 7–56 and time to culture conversion in rifampicin-susceptible tuberculosis (hazard ratio: 1.7; 95% CI 1.1–2.7), but not at end of treatment in one study. This study was stopped due to serious hepatotoxic adverse events, including three deaths, in 4% (95% CI 2–8) patients on pretomanid–moxifloxacin–pyrazinamide and none in controls. In patients with uncomplicated rifampicin-resistant tuberculosis on pretomanid-moxifloxacin-pyrazinamide treatment, 91% (95% CI 59–100) had favourable end-of-treatment outcomes. In patients with highly resistant tuberculosis, 90% (95% CI 83–95) on pretomanid–bedaquiline–linezolid had favourable outcomes six months after treatment, but linezolid-related toxicity was frequent. No acquired resistance to pretomanid was reported.

Conclusions

Evidence suggests an important role for pretomanid in rifampicin-resistant and highly resistant tuberculosis. Trials comparing pretomanid to existing core and companion drugs are needed to further define that role.

中文翻译：

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Pretomanid 治疗结核病：系统评价

背景

尚未系统评价使用包括 pretomanid 在内的方案治疗结核病患者的结果。

目标

评估现有的关于 pretomanid 在结核病中的疗效和安全性的证据。

数据源

Pubmed，clinicaltrials.gov。和 Cochrane 图书馆。

研究资格标准

提供有关 pretomanid 临床疗效或安全性的原始数据的定量研究。

参与者

结核病患者。

干预措施

在至少一个研究组中使用 pretomanid 或含有 pretomanid 的方案进行治疗。

方法

两位作者独立提取数据并评估偏倚风险。疗效（早期杀菌活性、杀菌活性、治疗结束结果和获得性耐药性）和安全性数据汇总在表格中。计算了不同研究方案之间疗效结果的平均差异。

结果

包括八项研究；四项关于利福平敏感结核病 2 周早期杀菌活性的随机对照试验、三项利福平敏感结核病随机试验和一个利福平耐药结核病组（两项关于 8 周杀菌活性，一项关于治疗结束）结果），一项在高耐药性结核病中具有治疗结束结果的单臂试验。pretomanid-莫西沙星-吡嗪酰胺在第 0-2、0-56 和 7-56 天菌落形成单位的每日变化以及利福平敏感结核病的培养转化时间方面优于标准治疗（风险比：1.7；95 % CI 1.1–2.7)，但在一项研究中不是在治疗结束时。该研究因严重的肝毒性不良事件而停止，包括三人死亡，在 4% (95% CI 2-8) 患者中使用 pretomanid-莫西沙星-吡嗪酰胺，而对照组中没有。在接受 pretomanid-莫西沙星-吡嗪酰胺治疗的简单利福平耐药结核病患者中，91% (95% CI 59-100) 的治疗结束结果良好。在高度耐药结核病患者中，90% (95% CI 83-95) 的 pretomanid-贝达喹啉-利奈唑胺治疗 6 个月后有良好的结果，但利奈唑胺相关的毒性很常见。没有报告对 pretomanid 的获得性耐药。90% (95% CI 83-95) 使用 pretomanid-贝达喹啉-利奈唑胺治疗 6 个月后有良好的结果，但利奈唑胺相关毒性很常见。没有报告对 pretomanid 的获得性耐药。90% (95% CI 83-95) 使用 pretomanid-贝达喹啉-利奈唑胺治疗 6 个月后有良好的结果，但利奈唑胺相关毒性很常见。没有报告对 pretomanid 的获得性耐药。

结论

有证据表明，pretomanid 在利福平耐药和高耐药结核病中具有重要作用。需要进行比较 pretomanid 与现有核心和伴随药物的试验，以进一步确定该作用。