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

Overview

Journal BMJ Open

Specialty General Medicine

Date 2014 Jan 4

PMID 24384902

Citations 26

Authors

Thomas J Hwang

Svetlana Dotsenko

Azizkhon Jafarov

Karin Weyer

Dennis Falzon

Kaspars Lunte

Paul Nunn

Ernesto Jaramillo

Salmaan Keshavjee

Douglas F Wares

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Adverse reactions induced by MDT/WHO (Rifampicin+Clofazimine+Dapsone) and ROM (Rifampicin+Ofloxacin+Minocycline) regimens used in the treatment of leprosy: a cohort study in a National Reference Center in Brazil.

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