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

• Published in: BMJ open 2014-01, Vol.4 (1), p.e004143
• Main Authors: Hwang, Thomas J, Dotsenko, Svetlana, Jafarov, Azizkhon, Weyer, Karin, Falzon, Dennis, Lunte, Kaspars, Nunn, Paul, Jaramillo, Ernesto, Keshavjee, Salmaan, Wares, Douglas F
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2013-004143

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.