Compassionate use of delamanid in adults and children for drug-resistant tuberculosis: 5-year update

Background: Although delamanid has been approved for the treatment of multidrug-resistant TB (MDR TB) in numerous regions, in areas where it is not yet registered it can be accessed as part of salvage therapy (in particular for those patients with limited treatment options) via the Otsuka compassionate use programme. Here we present the analysis of interim treatment outcomes by 24 weeks of more than 200 MDR-TB patients globally who received delamanid under this programme. Methods: We evaluated treatment efficacy with respect to culture negativity at 24 weeks, as well as the safety profile of delamanid, in an MDR-TB patient cohort treated under compassionate use between 2014 and 2019. Results: Among patients who received delamanid as part of a multidrug regimen, 123 (61%) out of 202 had extensively drug-resistant TB (XDR-TB), 66 (33%) out of 202 had HIV co-infection and 34 (17%) out of 202 were children aged between 6 and 17 years. Of those patients who were culture positive at delamanid treatment initiation and who completed 24 weeks of delamanid treatment in combination with other anti-tuberculosis (TB) drugs, culture negativity was achieved in 116 (79%) out of 147 cases. The corresponding rates of culture negativity for patients with XDR-TB and HIV co-infection, as well as the paediatric subgroup were 69 (77%) out of 90, 44 (92%) out of 48 and 20 (80%) out of 25, respectively. QT interval prolongation was the most frequently observed serious adverse event and was reported in 8% of patients receiving delamanid. Overall, treatment safety outcomes did not reveal any new or unidentified risks. Conclusions: The use of delamanid combined with other active drugs has the potential to achieve high rates of culture negativity in difficult-to-treat drug-resistant TB cases, with a favourable safety profile.