Real-world effectiveness and safety of prolonged bedaquiline course in the treatment of drug-resistant tuberculosis-a multi-center retrospective cohort study in a country with a high burden of drug-resistant tuberculosis.

Abstract

Bedaquiline (BDQ) has gradually become a core drug in drug-resistant tuberculosis (DR-TB) treatment, and the additional benefits of prolonging BDQ use remain unclear. Patients with DR-TB who received a BDQ-containing regimen from three Chinese clinical centers between 1 March 2018 and 31 December 2021 were retrospectively analyzed. Treatment outcomes and adverse drug reactions were compared between 6-month and prolonged BDQ treatment group before and after adjustment by propensity score matching (PSM). A total of 160 patients were enrolled, 72 patients were treated with BDQ for 6 months, and 88 patients were over 6 months, of which the median duration was 9 months (IQR: 8-11 months). After PSM adjustment, there were no significant differences in treatment outcome between the prolonged groups (7-9, 10-12, >12 months) and the 6-month group (all P > 0.05). A total of 35 patients met the criteria for BDQ prolongation but did not receive it, resulting in a success rate of 60%, significantly lower than the prolonged group (78.4%, P = 0.038); however, after adjustment by PSM, there was no statistically significance (P > 0.05). The median treatment duration (23 months, IQR: 18.50-25.00 months) was significantly longer than the prolonged group (18 months, IQR: 15.00-20.25 months, P < 0.001). Additionally, two deaths occurred in the prolonged group, and none in the 6-month group. The cause of death in one patient was adjudicated as anti-TB treatment-related, while the other one was considered not. There were no significant differences in the effectiveness and safety between 6-month and prolonged group, it's still recommended to prolong BDQ use under close monitoring when anti-TB drugs are insufficient to form an effective treatment regimen. Prolonged use of BDQ achieved similar treatment outcomes while potentially shortening the overall anti-TB duration.IMPORTANCEThis real-world retrospective cohort study provides critical evidence on the extended application of Bedaquiline (BDQ) in managing drug-resistant tuberculosis (DR-TB). To date, the effectiveness and safety data regarding prolonged BDQ treatment are still lacking, and the additional benefits of prolonged BDQ use remain unclear. Our findings notably demonstrate that prolonged use of BDQ can achieve similar treatment success rates while potentially shortening the overall anti-TB treatment duration. We conclude that when the anti-TB drugs are insufficient to form an effective treatment regimen, prolonged BDQ use with rigorous safety monitoring is recommended. Our study significantly advances the evidence base for prolonged use of BDQ in clinical practice.