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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Fixed and random effects meta-analysis of cohort studies and systematic review.
  
  
  METHODS
  Electronic and manual searches were combined.
  
  
  METHODS
  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.
authors.affiliation: Faculty of Arts and Sciences, Harvard University, Cambridge, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hwang
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dotsenko
authors.forename: Azizkhon
authors.initials: A
authors.lastname: Jafarov
authors.forename: Karin
authors.initials: K
authors.lastname: Weyer
authors.forename: Dennis
authors.initials: D
authors.lastname: Falzon
authors.forename: Kaspars
authors.initials: K
authors.lastname: Lunte
authors.forename: Paul
authors.initials: P
authors.lastname: Nunn
authors.forename: Ernesto
authors.initials: E
authors.lastname: Jaramillo
authors.forename: Salmaan
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Wares
mesh_terms: D002991:Clofazimine / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D006801:Humans; D007917:Leprostatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D007917:Leprostatic Agents; D002991:Clofazimine
keywords: Infectious Diseases