Establishing the Safety and Efficacy of Bedaquiline-Containing Regimen for the Treatment of Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

The risks and benefits of bedaquiline (BDQ) for treatment of drug-resistant tuberculosis (DR-TB) have not been firmly established. We aimed to assess the safety and efficacy of BDQ-containing regimens for the treatment of DR-TB as evidenced in available randomized controlled trials (RCTs). In this systematic review and meta-analysis, five databases (i.e., ClinicalTrials.gov, Cochrane CENTRAL, PubMed, ScienceDirect, and SinoMed) were searched. RCTs among DR-TB patients that had a control arm were eligible. The safety endpoints were all-cause mortality and serious adverse effects (SAEs). Efficacy outcomes were sputum culture conversion rate at 8-12 weeks and 24-26 weeks, treatment success, and time to culture conversion. A total of 476 records were screened; 18 met the eligibility criteria. The pooled analysis included 2520 participants (55.8% received BDQ-containing regimens, n=1408). Pooled safety outcomes showed no significant reduction in all-cause mortality (relative risk [RR] 95%confidence interval CI=0.94 [0.41-2.20]) or SAEs (RR 95%CI=0.91 [0.67-1.23]) in the BDQ-regimen group. Pooled efficacy outcomes showed significantly superior culture conversion rates at 8-12 weeks (RR 95%CI=1.35 [1.10-1.65]) and 24-26 weeks (RR 95%CI=1.25 [1.15-1.36]), more treatment success (RR 95%CI=1.30 [1.17-1.44]), and a 17-day reduction in the time to culture conversion (standardized mean difference [SMD] 95%CI=-17.46 [-34.82 to -0.11]) in the BDQ-regimen group (reference: non-BDQ regimen). Overall, BDQ regimens showed significant treatment effect against DR-TB but did not reduce mortality or SAEs.