The efficacy and safety of bedaquiline in the treatment of pulmonary tuberculosis patients: a systematic review and meta-analysis

Abstract

Abstract Background The World Health Organization (WHO) recommends bedaquiline (BDQ) as a Group A drug for the treatment of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of BDQ-containing regimens for the treatment of pulmonary TB patients. Methods MEDLINE (PubMed), EBSCO, the Cochrane Central Register of Controlled Trials and CNKI (China National Knowledge Infrastructure) were searched to identify eligible trials until September 8, 2022, for randomized controlled trials (RCTs) and non-randomized studies (NRSs) where BDQ was administered to patients with TB. Outcomes of interest were: (1) efficacy, including the rate of sputum culture conversion at 8 weeks, 24 weeks, and follow-up, and the rate of complete, cure, death, failure, and lost to follow-up at end of the treatment. (2) safety, which includes the incidence of cardiotoxicity, hepatotoxicity, and grade 3–5 adverse events during the treatment. Results A total of 29 articles (N = 23,358) fulfilled the eligibility criteria and were included in the meta-analysis. Compared with the BDQ-unexposed patients, The BDQ-containing regimen improved the rate of sputum conversion in RCTs (24 weeks: RR = 1.27, 95%Cl:1.10 to 1.46, follow-up: RR = 1.33, 95%Cl:1.06 to 1.66) and increased cure rate (RR = 1.60, 95%Cl: 1.13 to 2.26), and it also decreased the failure rate by 0.56 (95%Cl: 0.56 to 0.88). In NRSs, BDQ-containing regimen improved the sputum culture conversion rate (follow-up: RR = 1.53, 95%Cl: 1.07 to 2.20) and the rate of cure (RR = 1.86,95%Cl:1.23 to 2.83), reduced the rate of all-cause death (RR = 0.68, M-H random-effects 95%Cl: 0.48 to 0.97) and failure (RR = 0.57, 95%Cl:0.46 to 0.71). In terms of safety, BDQ-containing regimen administration increased the incidence of cardiotoxicity (RR = 4.54, M-H random-effects 95%Cl: 1.74–11.87) and grade 3–5 adverse events (RR = 1.42, M-H random-effects 95%Cl: 1.17–1.73) in RCTs; NRSs showed cardiotoxicity was associated with BDQ-containing regimen (RR = 6.00, M-H random-effects 95%Cl: 1.32–27.19). In the other outcomes, there was no significant difference between the intervention and control groups. Conclusions RCTs and NRSs data support the efficacy of BDQ for pulmonary TB, but cardiotoxicity and serious adverse events of BDQ were frequent. Overall, there is a lack of comparative data on efficacy and safety. Due to the serious risk of bias and discrepancy, further confirmation is needed.