Signal mining and analysis of adverse events of Brentuximab Vedotin base on FAERS and JADER databases

OBJECTIVES: Brentuximab Vedotin (BV) is a novel antibody-drug conjugate (ADC) approved for the treatment of classical Hodgkin's lymphoma and systemic anaplastic large cell lymphoma. However, as a relatively new therapeutic agent, the long-term safety profile and adverse event (AE) profile of BV require further investigation. This study aimed to identify significant and unexpected AEs associated with BV using data from the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases. METHODS: Data on BV-related AEs were extracted from the FAERS and JADER databases. Signal detection was performed using the reporting odds ratio (ROR) and 95% confidence intervals (95% CI). Risk signals were categorized according to system organ classes (SOCs) and preferred terms (PTs) as defined by the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. In addition, the onset times of BV-related AEs were analyzed. RESULTS: Between 2004 and 2023, a total of 19,279 and 2,561 AEs related to BV were recorded in the FAERS and JADER databases, respectively. At the SOC level, prominent signals in the FAERS database included blood and lymphatic system disorders, benign, malignant, and unspecified neoplasms (including cysts and polyps), as well as congenital, familial, and genetic disorders. In the JADER database, the most notable signals involved benign, malignant, and unspecified neoplasms, blood and lymphatic system disorders, and nervous system disorders. At the PT level, the top five signals in the FAERS database were peripheral motor neuropathy, peripheral sensory neuropathy, pneumocystis jirovecii pneumonia, febrile bone marrow aplasia, and polyneuropathy. Unexpected AEs included febrile bone marrow aplasia and Guillain-Barré syndrome. In the JADER database, the top five signals included peripheral motor neuropathy, peripheral sensory neuropathy, bacterial gastroenteritis, febrile neutropenia and pneumonia, with unexpected AEs such as left ventricular dysfunction, cardiomegaly, retinal detachment, and marasmus. The median onset time of AEs was 22 days (interquartile range [IQR] 7-81 days) in FAERS and 27 days (IQR 7-73 days) in JADER. CONCLUSION: The signal detection results from the FAERS and JADER databases highlight the importance of monitoring significant and unexpected AEs associated with BV, particularly in the early stages of treatment. These findings contribute to enhancing the post-marketing safety profile of BV and offer valuable insights for clinical risk management strategies.