Safety and availability of clofazimine in the treatment of multidrug and extensively drug-resistant tuberculosis: analysis of published guidance and meta-analysis of cohort studies
Safety and availability of clofazimine in the treatment of multidrug and extensively drug-resistant tuberculosis: analysis of published guidance and meta-analysis of cohort studies
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DOI：
10.1136/bmjopen-2013-004143
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发表时间：
2014-01-01
期刊：
影响因子：
2.9
通讯作者：
Wares, Douglas F.
中科院分区：
文献类型：
--
作者：
Hwang, Thomas J.;Dotsenko, Svetlana;Wares, Douglas F.
目的：鉴于耐多药结核病（MDR-TB）的蔓延，迫切需要新的治疗方法，包括重新利用现有药物。我们的目的是评估氯法齐明（Cfz），一种目前用于治疗麻风病的具有抗分枝杆菌活性的riminophenazine的临床和程序使用的关键考虑因素。设计：队列研究和系统回顾的固定和随机效应荟萃分析。设置：电子和手动检索相结合。纳入标准：用Cfz或含Cfz方案治疗耐多药和极耐药结核病的观察性研究，结果：5项观察性研究共纳入861例患者，其中602例接受了Cfz治疗。需要终止Cfz治疗的药物不良反应的汇总比例为0.1%（95% CI（0.0 - 0.6%）），所有不良事件的中位频率为5.1%。Cfz显示出体外抗结核分枝杆菌的有效性，含Cfz的方案可能在治疗耐药菌株患者和替代治疗选择有限的患者中发挥有用的作用。然而，头孢噻肟的吸收仍不足以满足全球需求;只有一家国际质量保证的制造商生产有限数量的优先用于治疗麻风病的药物，麻风病是该药物注册的唯一适应症。虽然数据有限，但Cfz与药物不良反应的风险相关，与一线结核病治疗相当，这是可以在方案条件下合理管理的。然而，市场供应不足和成本高是耐多药结核病患者获得Cfz的重要障碍。
Objectives: Given the spread of multidrug-resistant tuberculosis (MDR-TB), new therapies are urgently needed, including the repurposing of existing drugs. We aimed to assess key considerations for the clinical and programmatic use of clofazimine (Cfz), a riminophenazine with antimycobacterial activity currently used to treat leprosy.Design: Fixed and random effects meta-analysis of cohort studies and systematic review.Setting: Electronic and manual searches were combined.Inclusion criteria: Observational studies on treatment of multidrug-resistant and extremely drug-resistant tuberculosis with Cfz or a Cfz-containing regimen, and published guidance and documents relating to cost and availability were eligible.Results: 5 observational studies enrolled 861 patients, of which 602 received Cfz. The pooled proportion of adverse drug reactions requiring discontinuation of Cfz treatment was 0.1% (95% CI (0.0 to 0.6%)), and the median frequency of all adverse events was 5.1%. Cfz showed in vitro efficacy against Mycobacterium tuberculosis, and Cfz-containing regimens may have had a useful role in the treatment of patients with drug-resistant strains and who had limited alternative treatment options. However, Cfz uptake remains insufficient to meet global needs; there is only one internationally quality-assured manufacturer, which produces a limited quantity of the drug prioritised for treatment of leprosy, the only indication for which the drug is registered.Conclusions: While the data were limited, Cfz was associated with a risk for adverse drug reactions comparable to that of first-line TB treatment, which could be reasonably managed under programmatic conditions. However, low market availability and high cost are important barriers to access to Cfz for patients with MDR-TB.