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Journal Article > Research

Safety of treatment regimens containing bedaquiline and delamanid in the endTB cohort

Hewison CCH, Khan UT, Bastard M, Lachenal N, Coutisson S, Osso E, Ahmed SM, Khan PY, Franke MF, Rich ML, Varaine FFV, Melikyan N, Seung KJ, Adenov MM, Adnan S, Danielyan N, Islam S, Janmohamed A, Karakozian H, Kimenye MK, Kirakosyan O, Kholikulov B, Krisnanda A, Kumsa A, Leblanc GJ, Lecca L, Nkuebe M, Mamsa S, Padayachee S, Thit P, Mitnick CD, Huerga H
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Abstract
RATIONALE
Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion.

OBJECTIVES
Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid.

METHODS
Multicentre (16 countries), prospective, observational study, reporting incidence and frequency of clinically relevant adverse events of special interest (AESI) amongst patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent.

RESULTS
Among 2296 patients, the most common clinically relevant AESIs were: peripheral neuropathy in 26.4%, electrolyte depletion in 26.0%, and hearing loss in 13.2% of patients. Per 1000 person-months of treatment, the incidence of these events was 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients who received injectables (N=925) and linezolid (N=1826) were most likely to experience events during exposure: Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95%CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure.

CONCLUSIONS
Adverse events often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring schedules and individual drug durations should reflect expected safety profiles of drug combinations.

CLINICAL TRIALS REGISTRATION
NCT02754765
Subject Area
antibiotic resistancetuberculosisantimicrobial resistance
Collections
The endTB project
DOI
10.1093/cid/ciac019
Published Date
15-Sep-2022
PubMed ID
35028659
Languages
English
Journal
Clinical Infectious Diseases
Volume / Issue / Pages
Volume 75, Issue 6, Pages 1006-1013
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