Abstract
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.
Abstract
This compassionate use programme constitutes one of the largest cohorts of TB patients treated with delamanid in a resource-limited, non-clinical trial setting https://bit.ly/3nDSw52
Footnotes
Data availability: To submit inquiries related to Otsuka clinical research, or to request access to individual participant data (IPD) associated with any Otsuka clinical trial, please visit https://clinical-trials.otsuka.com/. For all approved IPD access requests, Otsuka will share anonymised IPD on a remotely accessible data sharing platform.
Conflict of interest: S. Ghosh is an employee of Otsuka Novel Products GmbH.
Conflict of interest: L. Breitscheidel reports being employed by Otsuka Novel Products GmbH, during the conduct of the Delamanid Compassionate Use Programme.
Conflict of interest: N. Lazarevic is an employee of Otsuka Novel Products GmbH.
Conflict of interest: A. Martin is an employee of Otsuka Novel Products GmbH.
Conflict of interest: J. Hafkin is an employee of Otsuka Pharmaceutical Development & Commercialisation, Inc.
Conflict of interest: N. Hittel is an employee of Otsuka Novel Products GmbH.
Support statement: Funding for the Otsuka Compassionate Use Programme was provided by Otsuka Novel Products GmbH, Munich, Germany. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 24, 2020.
- Accepted November 13, 2020.
- Copyright ©ERS 2021.