Safety, Efficacy and Pharmacokinetics of daily optimised doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis
Espinosa-Pereiro, Juan (Hospital Universitari Vall d'Hebron)
Aguiar, Ana (Universidade do Porto)
Nara, Eva (Instituto de Investigaciones en Ciencias de la Salud - Department of Molecular Biology and Biotechnology, Asunción)
Medina, Angelica (National Program for Tuberculosis, Ministry of Health, Asunción)
Molinas, Gladys (Instituto Nacional de Enfermedades Respiratorias y Ambientales, Asunción)
Tavares, Margarida (Universidade do Porto)
Tórtola Fernández, María Teresa (Hospital Universitari Vall d'Hebron)
Ghimire, Samiksha (University of Groninguen)
Alfenaar, Jan-Willem C. (University of Groninguen)
Sturkenboom, Marieke G. G (University of Groninguen)
Magis-Escurra, Cecile (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC))
Sánchez-Montalvá, Adrián (Hospital Universitari Vall d'Hebron)
Barros, Henrique (Universidade do Porto)
Duarte, Raquel (Universidade do Porto)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2025
Abstract:	Background: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis without compromising the safety of patients. Methods: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics. We performed a Bayesian network meta-analysis (NMA) using a random-effects model. Results: In 19 studies, 2033 out of 3654 participants received rifampicin doses higher than 10mg/kg/day. The NMA showed an increased risk of overall and hepatic AE for the 40mg/kg/day dose (RR 4. 8, 95% CrI 1. 1; 25, and 15. 00, 95% CrI 1. 1; 58. 0, respectively), but no other doses, including 50mg/kg/day showed such an increase. Increasing doses improved sputum culture conversion at week 8 (RR 1. 3, 95% CrI 1. 1; 1. 7 for SCC with 35mg/kg/day). Conclusion: Optimal doses of rifampicin may be between 25 and 35mg/kg/day, but should be tailored at the individual or, at least, at the population level.
Grants:	Instituto de Salud Carlos III CM22/00246 European Commission 823890
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Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Tuberculosis ; Rifampicin ; Systematic review ; Network meta-analysis ; Clinical trials
Published in:	Oxford Academic, (January 2025)

DOI: 10.1093/cid/ciaf003

Available from: 2026-01-10 Postprint

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