Journal Article

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

Nunn, Paul, Keshavjee, Salmaan, Hwang, Thomas J, Dotsenko, Svetlana, Lunte, Kaspars, Weyer, Karin, Jafarov, Azizkhon, Jaramillo, Ernesto, Falzon, Dennis, Wares, Douglas F

2014

Overview

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.

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Clofazimine - adverse effects / Clofazimine - therapeutic use / Cohort Studies / Extensively Drug-Resistant Tuberculosis - drug therapy / Global Health / Humans / Leprostatic Agents - adverse effects / Leprostatic Agents - therapeutic use / Practice Guidelines as Topic / Systematic review / Tuberculosis, Multidrug-Resistant - drug therapy