The Efficacy and Safety of Bedaquiline in the Treatment of Pulmonary Tuberculosis Patients: A Systematic Review and Meta-Analysis.

Background: Bedaquiline (BDQ) has been designated as a Group A drug by the World Health Organization (WHO) for the management of multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This systematic review and meta-analysis aim to evaluate the efficacy and safety of BDQ-containing regimens for the treatment of patients with pulmonary TB.

Methods: PubMed (MEDLINE), Elton B. Stephens Company (EBSCO) database, the Cochrane Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) database were initially searched on 15 June 2022 and again on 20 March 2023. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) that administered BDQ to TB patients. The outcomes of interest were as follows: (1) efficacy, including the rate of sputum culture conversion at 8 weeks, 24 weeks, and during follow-up, as well as the rates of completion cure, death, treatment failure, and loss at follow-up and at the end of the treatment; and (2) safety, which encompassed the incidences of cardiotoxicity, hepatotoxicity, and grade 3-5 adverse events during the treatment period.

Results: A total of 29 articles were included in this meta-analysis, representing 23,358 individuals. Patients who were treated with BDQ were compared with patients who were not exposed to BDQ. The use of BDQ-containing regimens demonstrated improved rates of sputum conversion in RCTs at 24 weeks (RR = 1.27, 95% CI: 1.10 to 1.46) and during follow-up (RR = 1.33, 95% CI: 1.06 to 1.66). Additionally, BDQ-containing regimens showed increased cure rates (RR = 1.60, 95% CI: 1.13 to 2.26) and decreased failure rates (RR = 0.56, 95% CI: 0.56 to 0.88). In NRSs, BDQ-containing regimens improved the sputum culture conversion rate during follow-up (RR = 1.53, 95% CI: 1.07 to 2.20), increased the rate of cure (RR = 1.86, 95% CI: 1.23 to 2.83), reduced deaths from all causes (RR = 0.68, 95% CI: 0.48 to 0.97), and reduced failure rates (RR = 0.57, 95% CI: 0.46 to 0.71). However, the use of BDQ-containing regimens was associated with increased incidences of cardiotoxicity (RR = 4.54, 95% CI: 1.74 to 11.87) and grade 3-5 adverse events (RR = 1.42, 95% CI: 1.17 to 1.73) in RCTs. NRSs also showed an association between BDQ-containing regimens and cardiotoxicity (RR = 6.00, 95% CI: 1.32 to 27.19). No significant differences were observed between intervention groups and control groups with respect to other outcomes.

Conclusions: Data from both RCTs and NRSs support the efficacy of BDQ for the treatment of pulmonary tuberculosis. However, the use of BDQ is associated with a higher incidence of cardiotoxicity and serious adverse events. Comparative data on efficacy and safety are limited, and further confirmation is required, due to potential bias and discrepancies in the available studies.