Compassionate Use of Delamanid in Adults and Children for Drug-resistant TB: 5-year Update

Background Although delamanid has been approved for the treatment of multidrug-resistant tuberculosis (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 (CU) programme. Here we present the analysis of interim treatment outcomes by 24 weeks of more than 200 multidrug-resistant tuberculosis (MDR-TB) patients globally who received delamanid under the Otsuka CU programme.

Methods We evaluated the treatment efficacy, with respect to culture negativity at 24 weeks, and safety profile of delamanid in a MDR-TB cohort of patients treated under CU between 2014 and 2019.

Results Among patients who received delamanid as part of a multidrug regimen, 123/202 (61%) had extensively drug-resistant tuberculosis (XDR-TB), 66/202 (33%) had HIV co-infection, and 34/202 (17%) were children ages between 6 and 17 years. Of those patients who were culture positive at delamanid treatment initiation and completed 24 weeks of delamanid treatment in combination with other anti-TB drugs, culture negativity was achieved in 116/147 (79%). The corresponding rates of culture negativity for patients with XDR-TB, HIV co-infection, and the paediatric subgroup were 69/90 (77%), 44/48 (92%), and 20/25 (80%), respectively. QT interval prolongation was the most frequently observed serious adverse event (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 tuberculosis cases, with a favourable safety profile.