Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis.
| Title: | Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis. |
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| Authors: | Trevisi L; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.; Hernán MA; CAUSALab, Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.; Mitnick CD; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.; Partners in Health, Boston, Massachusetts.; Khan U; Interactive Research and Development Global, Singapore, Singapore.; Seung KJ; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.; Partners in Health, Boston, Massachusetts.; Rich ML; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.; Partners in Health, Boston, Massachusetts.; Bastard M; Field Epidemiology Department, Epicentre, Paris, France.; Huerga H; Field Epidemiology Department, Epicentre, Paris, France.; Melikyan N; Field Epidemiology Department, Epicentre, Paris, France.; Atwood SA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.; Avaliani Z; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.; Llanos F; Unidad de Tuberculosis, Hospital Nacional Dos de Mayo, Lima, Peru.; Instituto de Investigaciones en Ciencias Biomedicas, Universidad Ricardo Palma, Lima, Peru.; Manzur-Ul-Alam M; Interactive Research and Development, Dhaka, Bangladesh.; Zarli K; Médecins sans Frontières, Yangon, Myanmar.; Binegdie AB; Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.; Adnan S; Indus Hospital and Health Network, Karachi, Pakistan.; Melikyan A; Médecins sans Frontières, Yerevan, Armenia.; Gelin A; Zanmi Lasante, Port-au-Prince, Haiti.; Isani AK; National Core Research Group, Stop TB Partnership, Islamabad, Pakistan.; Vetushko D; Republican Scientific and Practical Centre of Pulmonology and Tuberculosis, Minsk, Belarus.; Daugarina Z; Astana City Center of Phthisiopulmonology, Astana, Kazakhstan.; Nkundanyirazo P; Partners in Health, Maseru, Lesotho.; Putri FA; Interactive Research and Development Global, Singapore, Singapore.; Vilbrun C; GHESKIO, Port-au-Prince, Haiti.; Khan M; Interactive Research and Development, Durban, South Africa.; Hewison C; Medical Department, Médecins sans Frontières, Paris, France; and.; Khan PY; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Franke MF; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts. |
| Source: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2023 Jun 01; Vol. 207 (11), pp. 1525-1532. |
| Publication Type: | Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 9421642 Publication Model: Print Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2000- : New York, NY : American Thoracic Society; Original Publication: New York, NY : American Lung Association, c1994- |
| MeSH Terms: | Antitubercular Agents*/therapeutic use ; Antitubercular Agents*/pharmacology ; Tuberculosis, Multidrug-Resistant*/drug therapy; Clofazimine/therapeutic use ; Diarylquinolines/therapeutic use ; Humans |
| Abstract: | Rationale: Current recommendations for the treatment of rifampicin- and multidrug-resistant tuberculosis include bedaquiline (BDQ) used for 6 months or longer. Evidence is needed to inform the optimal duration of BDQ. Objectives: We emulated a target trial to estimate the effect of three BDQ duration treatment strategies (6, 7-11, and ⩾12 mo) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis. Methods: To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse probability weighting. Measurements and Main Results: The 1,468 eligible individuals received a median of 4 (interquartile range, 4-5) likely effective drugs. In 87.1% and 77.7% of participants, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment was 0.85 (95% confidence interval [CI], 0.81-0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73-0.81) for 7-11 months, and 0.86 (95% CI, 0.83-0.88) for ⩾12 months. Compared with 6 months of BDQ, the ratio of treatment success was 0.91 (95% CI, 0.85-0.96) for 7-11 months and 1.01 (95% CI, 0.96-1.06) for ⩾12 months. Naive analyses that did not account for bias revealed a higher probability of successful treatment with ⩾12 months (ratio, 1.09 [95% CI, 1.05-1.14]). Conclusions: BDQ use beyond 6 months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time bias can influence estimates of the effects of treatment duration. Future analyses should explore the effect of treatment duration of BDQ and other drugs in subgroups with advanced disease and/or receiving less potent regimens. |
| Comments: | Comment in: Am J Respir Crit Care Med. 2023 Jun 1;207(11):1423-1424. doi: 10.1164/rccm.202303-0373ED.. (PMID: 37043826) |
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| Grant Information: | R01 AI146095 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: duration; endTB observational study; inverse probability weighting; rifampicin-resistant TB; target trial |
| Substance Nomenclature: | 0 (Antitubercular Agents); 78846I289Y (bedaquiline); D959AE5USF (Clofazimine); 0 (Diarylquinolines) |
| Entry Date(s): | Date Created: 20230221 Date Completed: 20230615 Latest Revision: 20240413 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10263131 |
| DOI: | 10.1164/rccm.202211-2125OC |
| PMID: | 36802336 |
| Database: | MEDLINE |
Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't