Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
14
05
2024
accepted:
30
09
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39477924
doi: 10.1038/s41467-024-53273-7
pii: 10.1038/s41467-024-53273-7
doi:
Substances chimiques
Rifampin
VJT6J7R4TR
rifapentine
XJM390A33U
Antitubercular Agents
0
Moxifloxacin
U188XYD42P
Types de publication
Journal Article
Clinical Trial, Phase III
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
9400Investigateurs
Harriet Mayanja Kizza
(HM)
Elias Ssaku
(E)
Isaac Sekitoleko
(I)
Joseph P Akol
(JP)
Andreas Diacon
(A)
Carmen Kleinhans
(C)
Julia Sims
(J)
Erika Mitchell
(E)
Bronwyn Hendricks
(B)
Yvetot Joseph
(Y)
Marie Jude Jean Louis
(MJJ)
Cadette Mercy
(C)
Alexandra Apollon
(A)
Gertrude Royal
(G)
Pamela Mukwekwerere
(P)
Yeukai Musodza
(Y)
Wilfred Gurupira
(W)
Michele Tameris
(M)
Angelique Kany Kany Luabeya
(AKK)
Mark Hatherill
(M)
Mario Camblart
(M)
Circée Phara Jean
(CP)
Mohammed Rassool
(M)
Noluthando Mwelase
(N)
Jaclyn Bennet
(J)
Lerato Mohapi
(L)
Ntebo Mogashoa
(N)
Debra Peters
(D)
Sanjay Gaikwad
(S)
Neetal Neverkar
(N)
Rahul Lokhande
(R)
Cornelius Munyanga
(C)
Mina Hosseinipour
(M)
Charity Potani
(C)
Elisha Okeyo
(E)
Samuel Gurrion Ouma
(SG)
Prisca Rabuogi
(P)
Rodrigo Escada
(R)
Lidiane Tuler
(L)
Johnstone Kumwenda
(J)
Kelvin Mponda
(K)
Lynne Cornelissen
(L)
Andriette Hiemstra
(A)
Umesh G Lalloo
(UG)
Sandy Pillay
(S)
Abraham Siika
(A)
Alberto Mendoza
(A)
Pedro Gonzales
(P)
Mey Leon
(M)
Javier R Lama
(JR)
Alvaro Schwalb
(A)
Eduardo Gotuzzo
(E)
Fredrick Sawe
(F)
Isaac Tsikhutsu
(I)
Sivaporn Gatechompol
(S)
Anchalee Avihingsanon
(A)
Natthapol Kosashunhanan
(N)
Patcharaphan Sugandhavesa
(P)
Marineide Gonçalves de Melo
(MG)
Rita de Cassia Alves Lira
(RC)
Anne Luetkemeyer
(A)
Carina Marquez
(C)
Kristine Coughlin
(K)
Kelly E Dooley
(KE)
Jacques H Grosset
(JH)
Eric L Nuermberger
(EL)
Lara Hosey
(L)
Anthony T Podany
(AT)
Andrey Borisov
(A)
Nicole Brown
(N)
Scott Burns
(S)
Crystal Carter
(C)
Lauren Cowan
(L)
Melinda Dunn
(M)
Barbara DeCausey
(B)
Melissa Fagley
(M)
Kimberly Hedges
(K)
Constance Henderson
(C)
Amanda Hott
(A)
Carla Jeffries
(C)
Katherine Klein
(K)
Joan Mangan
(J)
Gerald Mazurek
(G)
Ruth Moro
(R)
Lakshmi Peddareddy
(L)
James Posey
(J)
Mary Reichler
(M)
Jessica Ricaldi
(J)
Claire Sadowski
(C)
Melisa Willby
(M)
Yan Yuan
(Y)
April C Pettit
(AC)
Lien T Luu
(LT)
Hanh T T Nguyen
(HTT)
Hung V Nguyen
(HV)
Hue T M Nguyen
(HTM)
Cyndy Merrifield
(C)
Matebogo Xaba
(M)
Maya Jaffer
(M)
Keitumetse Majoro
(K)
Kwok-Chiu Chang
(KC)
Chi Chiu Leung
(CC)
Polo Pavon
(P)
Rogelio Duque
(R)
George Samuel
(G)
Joseph Burzynski
(J)
Mascha Elskamp
(M)
Jill Campbell
(J)
Marlon Quintero
(M)
Elizabeth Guy
(E)
Informations de copyright
© 2024. The Author(s).
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