Comparative safety of bedaquiline and delamanid in patients with multidrug resistant tuberculosis: A nationwide retrospective cohort study.
Bedaquiline
Delamanid
Drug-resistant tuberculosis
Pharmacoepidemiology
Journal
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
ISSN: 1995-9133
Titre abrégé: J Microbiol Immunol Infect
Pays: England
ID NLM: 100956211
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
14
11
2022
revised:
27
03
2023
accepted:
20
04
2023
medline:
14
8
2023
pubmed:
19
5
2023
entrez:
18
5
2023
Statut:
ppublish
Résumé
Bedaquiline and delamanid were recently approved for multidrug resistant tuberculosis (MDR-TB). Bedaquiline carries a black box warning of increased risk of death compared to the placebo arm, and there is a need to establish the risks of QT prolongation and hepatotoxicity for bedaquiline and delamanid. We retrospectively analyzed data of MDR-TB patients retrieved from the South Korea national health insurance system database (2014-2020) to assess the risks of all-cause death, long QT-related cardiac event, and acute liver injury associated with bedaquiline or delamanid, compared with conventional regimen. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Stabilized inverse probability of treatment weighting based on propensity score was used to balance characteristics between the treatment groups. Of 1998 patients, 315 (15.8%) and 292 (14.6%) received bedaquiline and delamanid, respectively. Compared with conventional regimen, bedaquiline and delamanid did not increase risk of all-cause death at 24-month (HR 0.73 [95% CI, 0.42-1.27] and 0.89 [0.50-1.60], respectively). Bedaquiline-containing regimen increased risk of acute liver injury (1.76 [1.31-2.36]), while delamanid-containing regimen increased risk of long QT-related cardiac events (2.38 [1.05-3.57]) within 6 months of treatment. This study adds to the emerging evidence refuting the higher mortality rate observed in the bedaquiline trial population. Association between bedaquiline and acute liver injury needs careful interpretation considering for other background hepatotoxic anti-TB drugs. Our finding on delamanid and long QT-related cardiac events suggest careful risk-benefit assessment in patients with pre-existing cardiovascular disease.
Sections du résumé
BACKGROUND/PURPOSE(S)
OBJECTIVE
Bedaquiline and delamanid were recently approved for multidrug resistant tuberculosis (MDR-TB). Bedaquiline carries a black box warning of increased risk of death compared to the placebo arm, and there is a need to establish the risks of QT prolongation and hepatotoxicity for bedaquiline and delamanid.
METHODS
METHODS
We retrospectively analyzed data of MDR-TB patients retrieved from the South Korea national health insurance system database (2014-2020) to assess the risks of all-cause death, long QT-related cardiac event, and acute liver injury associated with bedaquiline or delamanid, compared with conventional regimen. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Stabilized inverse probability of treatment weighting based on propensity score was used to balance characteristics between the treatment groups.
RESULTS
RESULTS
Of 1998 patients, 315 (15.8%) and 292 (14.6%) received bedaquiline and delamanid, respectively. Compared with conventional regimen, bedaquiline and delamanid did not increase risk of all-cause death at 24-month (HR 0.73 [95% CI, 0.42-1.27] and 0.89 [0.50-1.60], respectively). Bedaquiline-containing regimen increased risk of acute liver injury (1.76 [1.31-2.36]), while delamanid-containing regimen increased risk of long QT-related cardiac events (2.38 [1.05-3.57]) within 6 months of treatment.
CONCLUSION
CONCLUSIONS
This study adds to the emerging evidence refuting the higher mortality rate observed in the bedaquiline trial population. Association between bedaquiline and acute liver injury needs careful interpretation considering for other background hepatotoxic anti-TB drugs. Our finding on delamanid and long QT-related cardiac events suggest careful risk-benefit assessment in patients with pre-existing cardiovascular disease.
Identifiants
pubmed: 37202241
pii: S1684-1182(23)00087-7
doi: 10.1016/j.jmii.2023.04.009
pii:
doi:
Substances chimiques
Antitubercular Agents
0
bedaquiline
78846I289Y
OPC-67683
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
842-852Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest J-YS received grants from the Ministry of Food and Drug Safety, Ministry of Health and Welfare, National Research Foundation of Korea, and pharmaceutical companies including Daiichi Sankyo, GSK and Pfizer outside the submitted work.