Efficacy and Tolerability of Concomitant Use of Bedaquiline and Delamanid for Multidrug- And Extensively Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

Publikation: Bidrag til tidsskriftReviewForskningfagfællebedømt

  • Freja Breth Holmgaard
  • Lorenzo Guglielmetti
  • Lillebæk, Troels
  • Åse Bengaard Andersen
  • Christian Wejse
  • Victor Naestholt Dahl
The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization–defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3–81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1–11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.
OriginalsprogEngelsk
TidsskriftClinical Infectious Diseases
Vol/bind76
Udgave nummer7
Sider (fra-til)1328-1337
Antal sider10
ISSN1058-4838
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Potential conflicts of interest . L. G. is a principal investigator of 2 phase III randomized controlled trials, funded by Unitaid and sponsored by Médecins Sans Frontières, testing shorter regimens for MDR/RR-TB including bedaquiline and delamanid. C. W. is on an advisory board for Pfizer on COVID-19 treatments (2 meetings in 2022 for which an honorarium was paid) and was recently lecturing on future pandemics for pulmonology specialists for Novartis (payment or honoraria). These sponsors had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript. All other authors report no potential conflicts.

Publisher Copyright:
© The Author(s) 2022.

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