Hwang Thomas J, Dotsenko Svetlana, Jafarov Azizkhon, Weyer Karin, Falzon Dennis, Lunte Kaspars, Nunn Paul, Jaramillo Ernesto, Keshavjee Salmaan, Wares Douglas F
Faculty of Arts and Sciences, Harvard University, Cambridge, USA.
BMJ Open. 2014 Jan 2;4(1):e004143. doi: 10.1136/bmjopen-2013-004143.
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.
Fixed and random effects meta-analysis of cohort studies and systematic review.
Electronic and manual searches were combined.
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.
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.
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.
鉴于耐多药结核病（MDR-TB）的传播，迫切需要新的治疗方法，包括对现有药物进行重新利用。我们旨在评估氯法齐明（Cfz）临床和项目使用的关键考虑因素，Cfz是一种具有抗分枝杆菌活性的吩嗪类药物，目前用于治疗麻风病。
队列研究的固定效应和随机效应荟萃分析及系统评价。
电子检索与手工检索相结合。
关于用Cfz或含Cfz方案治疗耐多药和广泛耐药结核病的观察性研究，以及与成本和可及性相关的已发表指南和文件均符合要求。
5项观察性研究纳入了861例患者，其中602例接受了Cfz治疗。因药物不良反应而需要停用Cfz治疗的汇总比例为0.1%（95%CI（0.0至0.6%）），所有不良事件的中位发生率为5.1%。Cfz在体外对结核分枝杆菌具有疗效，含Cfz方案在治疗耐药菌株患者以及替代治疗选择有限的患者中可能发挥了有益作用。然而，Cfz的使用量仍不足以满足全球需求；只有一家具有国际质量保证的制造商，该制造商生产的药物数量有限，且优先用于治疗麻风病，这是该药物唯一注册的适应证。
虽然数据有限，但Cfz与一线结核病治疗相当的药物不良反应风险相关，在项目条件下可合理控制。然而，低市场可及性和高成本是耐多药结核病患者获得Cfz的重要障碍。
