Incidence and risk factors of adverse drug reactions in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) regimens containing new drugs: a retrospective study of two national multicenter cohorts.

BACKGROUND: Treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) faces severe challenges, including prolonged courses, marked drug toxicity, and poor patient compliance. While regimens containing new drugs (bedaquiline, delamanid) have substantially improved MDR/RR-TB outcomes, systematic research on the epidemiological characteristics and risk control of adverse drug reactions (ADRs) remains insufficient. This study, based on a national multi-center clinical cohort, retrospectively analyzed data from 2,151 patients, aiming to explore the characteristics and risk factors related to ADR and provide a basis for individualized treatment.

METHODS: This study retrospectively included 2,151 patients with MDR/RR-TB from two national multicenter clinical cohorts in China (including the bedaquiline cohort and the delamanid cohort) from 2017 to 2022. Clinical data were extracted using a standardized process, and patients with missing key data that could not be traced were excluded from the study. Adverse reactions were defined and graded. Potential risk factors were screened through univariate analysis (Chi-squared test), and independent risk factors for ADRs were identified using a multivariate logistic regression model. The association between different types of ADRs and treatment drugs was also analyzed.

RESULTS: Overall ADR incidence was 56.2% (62.2% in bedaquiline cohort. 45.7% in delamanid cohort). The most common ADRs were cardiovascular [29.1%, mainly corrected QT interval (QTc) prolongation], hepatic (20.9%), and hematological (12.6%). Independent risk factors included female sex [odds ratio (OR) =1.26], age &#x2265;35 years (OR =1.31), body mass index <18.5 kg/m(OR =1.22), diabetes (OR =1.28), retreatment (OR =1.28), extrapulmonary TB (OR =1.62), cavitation (OR =1.24), and pre-extensively drug-resistant (XDR)/XDR-TB (OR =1.14/1.29). Both drugs were linked to QTc prolongation.

CONCLUSIONS: New MDR/RR-TB regimens are effective but carry a high ADR burden. Enhanced monitoring of high-risk groups and QTc/liver function is essential.