Comparative efficacy and safety of high-dose rifamycin regimens for tuberculosis treatment: a Bayesian network meta-analysis.

OBJECTIVES: High-dose rifamycin (HDR) regimens have demonstrated significant potential in tuberculosis (TB) treatment. This study aims to evaluate the efficacy and safety profile of different HDR regimens.

DESIGN: Using a systematic review and Bayesian network meta-analysis (NMA).

DATA SOURCES: PubMed, Web of Science, Cochrane Library and Embase were searched up to 2 November 2024.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials that compared the efficacy and safety of HDR regimens (rifampin 15-30 mg/kg/day and rifapentine 7.5-20 mg/kg/day) to standard-dose rifampin in patients with pulmonary drug-susceptible TB were included.

DATA EXTRACTION AND SYNTHESIS: The risk of bias was assessed using Cochrane tools. We conducted NMA with GEMTC in R. The simulation was performed using the Markov Chain Monte Carlo technique set on four parallel chains, with 20 000 burn-in iterations, 50 000 inference iterations and a thinning factor of n=2.5. To check for model convergence, Gelman and Rubin diagnostic plots and density plots were applied. We assessed heterogeneity using the I² test, evaluated transitivity by comparing effect modifiers across studies and examined consistency via node-splitting analysis. The confidence in network meta-analysis online tool and Cochrane Risk of Bias 2.0 Tool were used to assess evidence certainty and risk of bias, respectively. Higher surface area under the cumulative rank curve scores indicated a higher probability of top-ranking treatments.

RESULTS: Out of 15 766 citations screened, 15 randomised controlled trials were included, encompassing 6456 subjects. The risk of bias was low in 14 studies, with some concerns in one. Patients receiving rifapentine 20 mg/kg/day (risk ratio, 1.09; 95% credible interval, 1.03 to 1.17) had higher culture conversion rates at 8 weeks in solid culture compared with the control. There was no significant difference in primary efficacy within all HDR regimens. Rifapentine 20 mg/kg/day was ranked as the most effective intervention for primary efficacy. No statistical difference in the incidence of serious adverse events was found between all regimens.

CONCLUSIONS: Rifapentine 20 mg/kg/day may be the most effective for achieving the strongest anti-TB activity. All HDR regimens demonstrated good safety.

PROSPERO REGISTRATION NUMBER: CRD42024504575.