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Journal Article > Research

Effectiveness of bedaquiline use beyond six months in patients with multidrug-resistant tuberculosis

Trevisi L, Hernán MA, Mitnick CD, Khan UT, Seung KJ, Rich ML, Bastard M, Huerga H, Melikyan N, Atwood S, Avaliani Z, Llanos F, Manzur-ul-Alam M, Zarli K, Binedgie AB, Adnan S, Melikyan A, Gelin A, Isani AK, Vetushko D, Daugarina Z, Nkundanyirazo P, Putri FA, Vilbrun C, Khan MA, Hewison CCH, Khan PY, Franke MF
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Abstract
RATIONALE
Current recommendations for the treatment of rifampin- and multidrug-resistant tuberculosis include bedaquiline used for six months or longer. Evidence is needed to inform the optimal duration of bedaquiline.

OBJECTIVES
We emulated a target trial to estimate the effect of three bedaquiline duration treatment strategies (6 months, 7-11 months, ≥ 12 months) 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.

MAIN RESULTS
The 1,468 eligible individuals received a median of four (IQR: 4-5) likely effective drugs. In 87.1% and 77.7%, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment (95% CI) was 0.85 (0.81, 0.88) for 6 months of BDQ, 0.77 (0.73, 0.81) for 7-11 months, and 0.86 (0.83, 0.88) for > 12 months. Compared with 6 months of bedaquiline, the ratio of treatment success (95% CI) was 0.91 (0.85, 0.96) for 7-11 months and 1.01 (0.96, 1.06) for > 12 months. Analyses that did not account for immortal time bias found a higher probability of successful treatment with > 12 months: ratio 1.09 (1.05, 1.14).

CONCLUSIONS
Bedaquiline use beyond six 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 can bias estimate of effects of treatment duration. Future analyses should explore the effect of duration of bedaquiline and other drugs in subgroups with advanced disease and/or receiving less potent regimens.
Subject Area
antibiotic resistancetuberculosisantimicrobial resistance
Collections
The endTB project
DOI
10.1164/rccm.202211-2125OC
Published Date
01-Jun-2023
PubMed ID
36802336
Languages
English
Journal
American Journal of Respiratory and Critical Care Medicine
Volume / Issue / Pages
Volume 207, Issue 11, Pages 1525-1532
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