Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis
Trevisi L. Hernán M.A. Mitnick C.D. Khan U. Seung K.J. Rich M.L. Bastard M. Huerga H. Melikyan N. Atwood S.A. Avaliani Z. Llanos F. Manzur-Ul-Alam M. Zarli K. Binegdie A.B. Adnan S. Melikyan A. Gelin A. Isani A.K. Vetushko D. Daugarina Z. Nkundanyirazo P. Putri F.A. Vilbrun C. Khan M. Hewison C. Khan P.Y. Franke M.F.
1 June 2023American Thoracic Society
American Journal of Respiratory and Critical Care Medicine
2023#207Issue 111525 - 1532 pp.
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. Copyright
duration , endTB observational study , inverse probability weighting , rifampicin-resistant TB , target trial
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Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, United States
CAUSALab, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, United States
Division of Global Health Equity, Brigham and Womens Hospital, Boston, MA, United States
Partners in Health, Boston, MA, United States
Interactive Research and Development Global, Singapore, Singapore
Field Epidemiology Department, Epicentre, Paris, France
National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia
Unidad de Tuberculosis, Hospital Nacional Dos de Mayo, Lima, Peru
Instituto de Investigaciones en Ciencias Biomedicas, Universidad Ricardo Palma, Lima, Peru
Interactive Research and Development, Dhaka, Bangladesh
Médecins Sans Frontières, Yangon, Myanmar
Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
Indus Hospital and Health Network, Karachi, Pakistan
Medécins sans Frontières, Yerevan, Armenia
Zanmi Lasante, Port-au-Prince, Haiti
National Core Research Group, Stop TB Partnership, Islamabad, Pakistan
Republican Scientific and Practical Centre of Pulmonology and Tuberculosis, Minsk, Belarus
Astana City Center of Phthisiopulmonology, Astana, Kazakhstan
Partners in Health, Maseru, Lesotho
GHESKIO, Port-au-Prince, Haiti
Interactive Research and Development, Durban, South Africa
Medical Department, Médecins sans Frontières, Paris, France
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
Department of Global Health and Social Medicine
CAUSALab
Division of Global Health Equity
Partners in Health
Interactive Research and Development Global
Field Epidemiology Department
National Center for Tuberculosis and Lung Diseases
Unidad de Tuberculosis
Instituto de Investigaciones en Ciencias Biomedicas
Interactive Research and Development
Médecins Sans Frontières
Department of Internal Medicine
Indus Hospital and Health Network
Medécins sans Frontières
Zanmi Lasante
National Core Research Group
Republican Scientific and Practical Centre of Pulmonology and Tuberculosis
Astana City Center of Phthisiopulmonology
Partners in Health
GHESKIO
Interactive Research and Development
Medical Department
Department of Clinical Research
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