The role of delamanid in the treatment of drug-resistant tuberculosis

Joseph M Lewis, Derek J Sloan, Joseph M Lewis, Derek J Sloan

Abstract

Tuberculosis (TB) remains a significant cause of death worldwide, and emergence of drug-resistant TB requires lengthy treatments with toxic drugs that are less effective than their first-line equivalents. New treatments are urgently needed. Delamanid, previously OPC-67863, is a novel drug of the dihydro-nitroimidazole class with potent anti-TB activity and great promise to be effective in the treatment of drug-resistant TB. This review examines the preclinical and clinical development of delamanid, reviews current guidance on its use and evaluates the opportunities and challenges for its future role in TB management.

Keywords: MDR-TB; OPC-67683; delamanid; drug resistance; tuberculosis.

Figures

Figure 1
Figure 1
Summary of the design and results of Phase IIb and observational studies of delamanid therapy. Notes:aDelamanid 100 mg, 200 mg, or placebo allocated by double-blind randomization; bdelamanid 100 mg or 200 mg allocated by treating physician. Data from Gler et al. Copyright European Respiratory Society©. This material has not been reviewed by European Respiratory Society prior to release; therefore the European Respiratory Society may not be responsible for any errors, omissions or inaccuracies, or for any consequences arising there from, in the content. Reproduced with permission of the European Respiratory Society: Eur Respir J. 2013;41:1393–1400; published ahead of print September 27, 2012, doi:10.1183/09031936.00125812. Abbreviations: OBR, optimized background regimen; WHO, World Health Organization.
Figure 2
Figure 2
Long-term outcome data on delamanid use from Trial 208 and Observational Study 116. Notes: In the analysis of all MDR-TB and XDR-TB patients, significantly more patients had favorable outcomes in the “long-term” delamanid group than those in the “short-term” group (P<0.001). In the analysis of only XDR-TB patients, there were more favorable outcomes in the “long-term” group but the difference did not reach statistical significance, perhaps because of the small sample size. However, there were significantly fewer deaths in the “long-term group” (P<0.001). Copyright European Respiratory Society©. This material has not been reviewed by European Respiratory Society prior to release; therefore the European Respiratory Society may not be responsible for any errors, omissions or inaccuracies, or for any consequences arising there from, in the content. Reproduced with permission of the European Respiratory Society: Eur Respir J. 2013;41:1393–1400; published ahead of print September 27, 2012, doi:10.1183/09031936.00125812. Abbreviations: MDR-TB, multidrug-resistant-tuberculosis; XDR-TB, extensively drug-resistant-tuberculosis.

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