Real-world safety profile of novel anti-multidrug-resistant tuberculosis drugs: a disproportionality analysis based on the FAERS database

Objectives Bedaquiline (BDQ), delamanid (DLM) and pretomanid (Pa) were widely used in recent years. This study aimed to analyse adverse drug event (ADE) reports associated with them based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to explore the signals of ADEs and provide reference for clinical use. Design A retrospective pharmacovigilance study. Setting The FAERS database was extracted from 2015 to 2023, and the ADE reports about BDQ, DLM, and Pa were collected. Main outcome measures Data mining was carried out on relevant reports of BDQ, DLM, and Pa using the reporting odds ratio (ROR), proportional reporting ratio (PRR), medicines and healthcare products regulatory agency (MHRA) and the information component (IC). Results A total of 4010 ADE reports were included: 2477 for BDQ, 1360 for DLM and 173 for Pa. Combined with disproportionality analysis in different backgrounds, the salient risks of three target drugs varied. In the entire dataset, prolonged ECG QT (BDQ: ROR=42.57; DLM: ROR=28.00; Pa: ROR=20.45), hepatitis toxic (BDQ: ROR=28.65; DLM: ROR=21.42; Pa: ROR=90.67), bilirubin conjugated increased (BDQ: ROR=14.40; DLM: ROR=14.56; Pa: ROR=53.95), increased aspartate aminotransferase (BDQ: ROR=9.10; DLM: ROR=8.83; Pa: ROR=7.77), increased alanine aminotransferase (BDQ: ROR=5.68; DLM: ROR=5.54; Pa: ROR=8.92), drug-induced liver injury (BDQ: ROR=6.51; DLM: ROR=6.24; Pa: ROR=3.61) and anaemia (BDQ: ROR=6.54; DLM: ROR=5.75; Pa: ROR=4.83) remained common risks for them. However, in the other two contexts, only decreased haemoglobin (tuberculosis dataset: ROR=2.15; target dataset: ROR=1.03), which was more pronounced associated with DLM and prolonged ECG QT (tuberculosis dataset: ROR=2.46; target dataset: ROR=1.23), hepatotoxicity (tuberculosis dataset: ROR=1.74; target dataset: ROR=4.03) was more pronounced associated with BDQ, while other ADEs, like pancreatitis (tuberculosis dataset: ROR=4.54; target dataset: ROR=7.36), death (tuberculosis dataset: ROR=5.71; target dataset: ROR=2.47) and multiple organ dysfunction syndrome (tuberculosis dataset: ROR=1.46; target dataset: ROR=2.76), were worthy of attention associated with Pa apart from the common ADEs. The combination of linezolid (LZD) with the target drugs elevated risk signals for hepatotoxicity, haematologic toxicity and neurotoxicity. Subgroup analyses revealed that Conclusion Our study highlights the differences in common ADEs of BDQ, DLM and Pa, as well as the differences in these ADEs among genders and age groups, providing valuable insights for clinical application.