Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort.
| Title: | Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort. |
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| Authors: | Hewison C; Medical Department, Médecins Sans Frontières, Paris, France.; Khan U; Interactive Research and Development Global, Singapore, Singapore.; Bastard M; Field Epidemiology Department, Epicentre, Paris, France.; Lachenal N; Pharmacovigilance Unit, Médecins Sans Frontières, Geneva, Switzerland.; Coutisson S; Pharmacovigilance Unit, Médecins Sans Frontières, Geneva, Switzerland.; Osso E; Partners In Health, Boston, Massachusetts, USA, and Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Ahmed S; Interactive Research and Development, Karachi, Pakistan.; Khan P; Interactive Research and Development Global, Singapore, Singapore.; Franke MF; Partners In Health, Boston, Massachusetts, USA, and Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Rich ML; Partners In Health, Boston, Massachusetts, USA, and Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Brigham and Women's Hospital, Boston, Massachusetts, USA.; Varaine F; Medical Department, Médecins Sans Frontières, Paris, France.; Melikyan N; Field Epidemiology Department, Epicentre, Paris, France.; Seung KJ; Partners In Health, Boston, Massachusetts, USA, and Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Brigham and Women's Hospital, Boston, Massachusetts, USA.; Adenov M; National Scientific Center of Phthisiopulmonology, MOH RK (NSCP MOH RK), Almaty, Kazakhstan.; Adnan S; Indus Health Network, Karachi, Pakistan.; Danielyan N; Medical Department, Médecins Sans Frontières, Tbilisi, Georgia.; Islam S; Interactive Research and Development, Dhaka, Bangladesh.; Janmohamed A; Interactive Research and Development, Karachi, Pakistan.; Karakozian H; Medical Department, Médecins Sans Frontières, Bishkek, Krygystan.; Kamene Kimenye M; National Tuberculosis Program, Nairobi, Kenya.; Kirakosyan O; Medical Department, Médecins Sans Frontières, Yerevan, Armenia.; Kholikulov B; Medical Department, Médecins Sans Frontières, Minsk, Belarus.; Krisnanda A; Aga Krisnanda, Interactive Research and Development, Jakarta, Indonesia.; Kumsa A; Partners In Health, Addis Ababa, Ethiopia.; Leblanc G; Zanmi Lasante, Cange, Haiti.; Lecca L; Socios En Salud Sucursal Peru, Lima, Peru.; Nkuebe M; Partners In Health, Maseru, Lesotho.; Mamsa S; Indus Health Network, Karachi, Pakistan.; Padayachee S; Interactive Research and Development, Durban, South Africa.; Thit P; Medical Department, Médecins Sans Frontières, Yangon, Myanmar.; Mitnick CD; Partners In Health, Boston, Massachusetts, USA, and Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Brigham and Women's Hospital, Boston, Massachusetts, USA.; Huerga H; Field Epidemiology Department, Epicentre, Paris, France. |
| Source: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2022 Sep 29; Vol. 75 (6), pp. 1006-1013. |
| Publication Type: | Journal Article; Observational Study; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: Jan. 2011- : Oxford : Oxford University Press; Original Publication: Chicago, IL : The University of Chicago Press, c1992- |
| MeSH Terms: | Nitroimidazoles*/therapeutic use ; Tuberculosis, Multidrug-Resistant*/drug therapy; Antitubercular Agents/adverse effects ; Diarylquinolines/adverse effects ; Electrolytes/therapeutic use ; Linezolid/adverse effects ; Oxazoles/adverse effects ; Humans ; Prospective Studies ; Treatment Outcome |
| Abstract: | 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: NCT02754765.; (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.) |
| Competing Interests: | Potential conflicts of interest. C. D. M. is a member of the Akagera Scientific Advisory Board for development of lipid-based, nanoparticle delivery of anti-tuberculosis (TB) drugs (one payment was made to Partners In Health as honorarium for this work). M. R. declared 5% of time spent on a National Institute of Allergy and Infectious Disease–sponsored grant, an observational study of multidrug-resistant TB treatment regimens, and 5% of time spent as an expert consultant on operational research for a World Health Organization EURO project S. P. reports being a subinvestigator on the Pragmatic Clinical Trial for a More Effective Concise and Less Toxic MDR-TB Treatment Regimen(s) (TB-PRACTECAL) trial, sponsored by Médecins Sans Frontières, as an employee of the Tuberculosis & HIV Investigative Network. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. |
| Comments: | Erratum in: Clin Infect Dis. 2023 Feb 18;76(4):779. doi: 10.1093/cid/ciac347.. (PMID: 36636798) |
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| Contributed Indexing: | Keywords: MDR-TB; QT prolongation; adverse events; linezolid; new drugs |
| Molecular Sequence: | ClinicalTrials.gov NCT02754765 |
| Substance Nomenclature: | 0 (Antitubercular Agents); 0 (Diarylquinolines); 0 (Electrolytes); 0 (Nitroimidazoles); 0 (OPC-67683); 0 (Oxazoles); 78846I289Y (bedaquiline); ISQ9I6J12J (Linezolid) |
| Entry Date(s): | Date Created: 20220114 Date Completed: 20221003 Latest Revision: 20230116 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9522425 |
| DOI: | 10.1093/cid/ciac019 |
| PMID: | 35028659 |
| Database: | MEDLINE |
Journal Article; Observational Study; Research Support, Non-U.S. Gov't