Safety, Efficacy and Pharmacokinetics of daily optimised doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis

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 recei...

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Detalles Bibliográficos
Autores: Espinosa-Pereiro, Juan|||0000-0002-7238-8337, Aguiar, Ana|||0000-0001-7841-7410, Nara, Eva, Medina, Angelica, Molinas, Gladys, Tavares, Margarida|||0000-0003-4518-2197, Tórtola Fernández, María Teresa|||0000-0002-9188-298X, Ghimire, Samiksha|||0000-0002-6028-1460, Alfenaar, Jan-Willem C., Sturkenboom, Marieke G. G.|||0000-0002-3420-0591, Magis-Escurra, Cecile|||0000-0001-8424-9425, Sánchez Montalvá, Adrián|||0000-0002-2194-5447, Barros, Henrique, Duarte, Raquel
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:308483
Acceso en línea:https://ddd.uab.cat/record/308483
https://dx.doi.org/urn:doi:10.1093/cid/ciaf003
Access Level:acceso abierto
Palabra clave:Tuberculosis
Rifampicin
Systematic review
Network meta-analysis
Clinical trials
Descripción
Sumario: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.

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