Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis

Guglielmetti L. Khan U. Velásquez G.E. Gouillou M. Abubakirov A. Baudin E. Berikova E. Berry C. Bonnet M. Cellamare M. Chavan V. Cox V. Dakenova Z. De Jong B.C. Ferlazzo G. Karabayev A. Kirakosyan O. Kiria N. Kunda M. Lachenal N. Lecca L. McIlleron H. Motta I. Toscano S.M. Mushtaque H. Nahid P. Oyewusi L. Panda S. Patil S. Phillips P.P.J. Ruiz J. Salahuddin N. Garavito E.S. Seung K.J. Ticona E. Trippa L. Vasquez D.E.V. Wasserman S. Rich M.L. Varaine F. Mitnick C.D.
30 January 2025 Massachussetts Medical Society

New England Journal of Medicine
2025 #392 Issue 5 468 - 482 pp.

Background For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis. Methods We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). Participants were randomly assigned (with the use of Bayesian response-adaptive randomization) to receive one of five combinations or standard therapy. The primary end point was a favorable outcome at week 73, defined by two negative sputum culture results or favorable bacteriologic, clinical, and radiologic evolution. The noninferiority margin was -12 percentage points. Results Among the 754 participants who underwent randomization, 699 were included in the modified intention-to-treat analysis, and 562 in the per-protocol analysis. In the modified intention-to-treat analysis, 80.7% of the patients in the standard-therapy group had favorable outcomes. The risk difference between standard therapy and each of the four new regimens that were found to be noninferior in the modified intention-to-treat population was as follows: BCLLfxZ, 9.8 percentage points (95% confidence interval [CI], 0.9 to 18.7); BLMZ, 8.3 percentage points (95% CI, -0.8 to 17.4); BDLLfxZ, 4.6 percentage points (95% CI, -4.9 to 14.1); and DCMZ, 2.5 percentage points (95% CI, -7.5 to 12.5). Differences were similar in the per-protocol population, with the exception of DCMZ, which was not noninferior in that population. The proportion of participants with grade 3 or higher adverse events was similar across the regimens. Grade 3 or higher hepatotoxic events occurred in 11.7% of participants overall and in 7.1% of those receiving standard therapy. Conclusions Consistent results across all the analyses support the noninferior efficacy of three all-oral shortened regimens for the treatment of rifampin-resistant tuberculosis.

Text of the article Перейти на текст статьи

Médecins Sans Frontières, Sorbonne Université, France
INSERM Unité 1135, Centre dImmunologie et des Maladies Infectieuses, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Universitaire, Sorbonne Université, France
Hôpital Pitié-Salpêtrière, Ctr. Natl. de Reference des Mycobacteries et de la Resistance des Mycobacteries Aux Antitu Berculeux, France
Epicentre, Paris, France
Translational Research on HIV and Endemic and Emerging Infectious Diseases, Montpellier Université de Montpellier, Institut de Recherche Pour le Développement, INSERM, Montpellier, France
Interactive Development and Research, Singapore
McGill University, Montreal, Canada
UCSF Center for Tuberculosis, United States
Division of HIV, Infectious Diseases, and Global Medicine, University of California at San Francisco, San Francisco, United States
National Scientific Center of Phthisiopulmonology, Kazakhstan
Center of Phthisiopulmonology of Almaty Health Department, Almaty, Kazakhstan
City Center of Phthisiopulmonology, Astana, Kazakhstan
Médecins Sans Frontières, London, United Kingdom
Medical Research Council, Clinical Trials Unit, University College London, London, United Kingdom
St. Georges University, London Institute for Infection and Immunity, London, United Kingdom
MedStar Health Research Institute, Washington, DC, United States
Médecins Sans Frontières, Mumbai, India
Indian Council of Medical Research Headquarters-New Delhi, New Delhi, India
Indian Council of Medical Research-National AIDS Research Institute, Pune, India
Centre for Infectious Disease Epidemiology and Research, South Africa
Department of Medicine, University of Cape Town, Cape Town, South Africa
Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa
Institute of Tropical Medicine, Antwerp, Belgium
Médecins Sans Frontières, Geneva, Switzerland
Médecins Sans Frontières, Yerevan, Armenia
National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia
Partners in Health, Maseru, Lesotho
Jhpiego Lesotho, Maseru, Lesotho
Socios en Salud Sucursal Peru, Lima, Peru
Hospital Nacional Sergio E. Bernales, Centro de Investigacion en Enfermedades Neumologicas, Lima, Peru
Hospital Nacional Dos de Mayo, Lima, Peru
Universidad Nacional Mayor de San Marcos, Lima, Peru
Hospital Nacional Hipólito Unanue, Lima, Peru
Harvard Medical School, Boston, United States
Partners in Health, Boston, United States
Division of Global Health Equity, Brigham and Womens Hospital, Boston, United States
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, United States
Harvard T.H. Chan School of Public Health, Boston, United States
Indus Hospital and Health Network, Karachi, Pakistan

Médecins Sans Frontières
INSERM Unité 1135
Hôpital Pitié-Salpêtrière
Epicentre
Translational Research on HIV and Endemic and Emerging Infectious Diseases
Interactive Development and Research
McGill University
UCSF Center for Tuberculosis
Division of HIV
National Scientific Center of Phthisiopulmonology
Center of Phthisiopulmonology of Almaty Health Department
City Center of Phthisiopulmonology
Médecins Sans Frontières
Medical Research Council
St. Georges University
MedStar Health Research Institute
Médecins Sans Frontières
Indian Council of Medical Research Headquarters-New Delhi
Indian Council of Medical Research-National AIDS Research Institute
Centre for Infectious Disease Epidemiology and Research
Department of Medicine
Wellcome Centre for Infectious Diseases Research in Africa
Institute of Tropical Medicine
Médecins Sans Frontières
Médecins Sans Frontières
National Center for Tuberculosis and Lung Diseases
Partners in Health
Jhpiego Lesotho
Socios en Salud Sucursal Peru
Hospital Nacional Sergio E. Bernales
Hospital Nacional Dos de Mayo
Universidad Nacional Mayor de San Marcos
Hospital Nacional Hipólito Unanue
Harvard Medical School
Partners in Health
Division of Global Health Equity
Department of Biostatistics and Computational Biology
Harvard T.H. Chan School of Public Health
Indus Hospital and Health Network

10 лет помогаем публиковать статьи Международный издатель

Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026