Risk-Stratified Treatment for Drug-Susceptible Pulmonary Tuberculosis

Authors

• Vincent K Chang
• Marjorie Z Imperial
• Patrick P J Phillips
• Gustavo E Velásquez
• Payam Nahid
• Andrew Vernon
• Ekaterina V Kurbatova
• Susan Swindells
• Richard E Chaisson
• Susan E Dorman
• John L Johnson
• Marc Weiner
• Amina Jindani
• Thomas Harrison
• Erin E Sizemore
• William Whitworth
• Wendy Carr
• Kia E Bryant
• Deron Burton
• Kelly E Dooley
• Melissa Engle
• Pheona Nsubuga
• Andreas H Diacon
• Nguyen Viet Nhung
• Rodney Dawson
• Radojka M Savic
• AIDS Clinical Trial Group
• Tuberculosis Trials Consortium

Language

English

Publication Date

10-30-2024

Journal

Nature Communications

DOI

10.1038/s41467-024-53273-7

PMID

39477924

PMCID

PMC11526018

PubMedCentral® Posted Date

10-30-2024

PubMedCentral® Full Text Version

Post-print

Abstract

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

Keywords

Humans, Rifampin, Tuberculosis, Pulmonary, Male, Female, Adult, Middle Aged, Antitubercular Agents, Moxifloxacin, Risk Factors, Treatment Outcome, Mycobacterium tuberculosis, Drug Therapy, Combination, Young Adult

Comments

This article has been corrected. See Nat Commun. 2025 May 13;16:4438.v

Published Open-Access

yes

Recommended Citation

Chang, Vincent K; Imperial, Marjorie Z; Phillips, Patrick P J; et al., "Risk-Stratified Treatment for Drug-Susceptible Pulmonary Tuberculosis" (2024). Faculty, Staff and Student Publications. 189.
https://digitalcommons.library.tmc.edu/uthdb_docs/189