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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
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 activi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902362/ https://www.ncbi.nlm.nih.gov/pubmed/24384902 http://dx.doi.org/10.1136/bmjopen-2013-004143 |
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author | Hwang, Thomas J Dotsenko, Svetlana Jafarov, Azizkhon Weyer, Karin Falzon, Dennis Lunte, Kaspars Nunn, Paul Jaramillo, Ernesto Keshavjee, Salmaan Wares, Douglas F |
author_facet | Hwang, Thomas J Dotsenko, Svetlana Jafarov, Azizkhon Weyer, Karin Falzon, Dennis Lunte, Kaspars Nunn, Paul Jaramillo, Ernesto Keshavjee, Salmaan Wares, Douglas F |
author_sort | Hwang, Thomas J |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3902362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39023622014-01-27 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 Hwang, Thomas J Dotsenko, Svetlana Jafarov, Azizkhon Weyer, Karin Falzon, Dennis Lunte, Kaspars Nunn, Paul Jaramillo, Ernesto Keshavjee, Salmaan Wares, Douglas F BMJ Open Global Health 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. BMJ Publishing Group 2014-01-02 /pmc/articles/PMC3902362/ /pubmed/24384902 http://dx.doi.org/10.1136/bmjopen-2013-004143 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Global Health Hwang, Thomas J Dotsenko, Svetlana Jafarov, Azizkhon Weyer, Karin Falzon, Dennis Lunte, Kaspars Nunn, Paul Jaramillo, Ernesto Keshavjee, Salmaan Wares, Douglas F 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Global Health |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902362/ https://www.ncbi.nlm.nih.gov/pubmed/24384902 http://dx.doi.org/10.1136/bmjopen-2013-004143 |
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