Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort

Hewison C. Khan U. Bastard M. Lachenal N. Coutisson S. Osso E. Ahmed S. Khan P. Franke M.F. Rich M.L. Varaine F. Melikyan N. Seung K.J. Adenov M. Adnan S. Danielyan N. Islam S. Janmohamed A. Karakozian H. Kamene Kimenye M. Kirakosyan O. Kholikulov B. Krisnanda A. Kumsa A. Leblanc G. Lecca L. Nkuebe M. Mamsa S. Padayachee S. Thit P. Mitnick C.D. Huerga H.
15 September 2022 Oxford University Press

Clinical Infectious Diseases
2022 #75 Issue 6 1006 - 1013 pp.

Background: Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. 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 (AESIs) among 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 (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 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 receiving 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: AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. Clinical Trials Registration: NCT03259269.

adverse events , linezolid , MDR-TB , new drugs , QT prolongation

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Medical Department, Medecins Sans Frontières, Paris, France
Interactive Research and Development Global, Singapore, Singapore
Field Epidemiology Department, Epicentre, Paris, France
Pharmacovigilance Unit, Medecins Sans Frontières, Geneva, Switzerland
Partners in Health, Boston, MA, United States
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, United States
Interactive Research and Development, Karachi, Pakistan
Brigham and Women s Hospital, Boston, MA, United States
National ScientificCenter of Phthisiopulmonology, MOH RK (NSCP MOH RK), Almaty, Kazakhstan
Indus Health Network, Karachi, Pakistan
Medical Department, Médecins Sans Frontières, GA, Tbilisi, Georgia
Interactive Research and Development, Dhaka, Bangladesh
Medical Department, Médecins Sans Frontières, Bishkek, Kyrgyzstan
National Tuberculosis Program, Nairobi, Kenya
Medical Department, Médecins Sans Frontières, Yerevan, Armenia
Medical Department, Médecins Sans Frontières, Minsk, Belarus
Aga Krisnanda, Interactive Research and Development, Jakarta, Indonesia
Partners in Health, Addis Ababa, Ethiopia
Zanmi Lasante, Haiti
Socios en Salud Sucursal Peru, Lima, Peru
Partners in Health, Maseru, Lesotho
Interactive Research and Development, Durban, South Africa
Medical Department, Médecins Sans Frontières, Yangon, Myanmar

Medical Department
Interactive Research and Development Global
Field Epidemiology Department
Pharmacovigilance Unit
Partners in Health
Department of Global Health and Social Medicine
Interactive Research and Development
Brigham and Women s Hospital
National ScientificCenter of Phthisiopulmonology
Indus Health Network
Medical Department
Interactive Research and Development
Medical Department
National Tuberculosis Program
Medical Department
Medical Department
Aga Krisnanda
Partners in Health
Zanmi Lasante
Socios en Salud Sucursal Peru
Partners in Health
Interactive Research and Development
Medical Department

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