Bedaquiline versus injectable containing regimens for rifampicin-resistant and multidrug-resistant tuberculosis in a reference center in Brazil - a real-world evidence study using a retrospective design.

Background: Drug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence.

Methods: Retrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute - Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis.

Results: Of the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36-5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14-0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62-3.57, p < 0.001), along with no illicit drug use and primary drug resistance.

Conclusions: The implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion.