A disproportionality analysis of adverse events caused by pexidartinib from the FDA adverse event reporting system

对来自FDA不良事件报告系统的pexidartinib引起的不良事件进行比例失衡分析

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Abstract

Tenosynovial giant cell tumor (TGCT) is a rare neoplasm closely associated with dysregulation of the colony-stimulating factor 1(CSF1)/CSF1R signaling pathway, faces high recurrence rates despite surgical intervention, prompting exploration of CSF1R inhibitors like pexidartinib. This retrospective pharmacovigilance study analyzed pexidartinib-associated adverse events (AEs) from FDA Adverse Event Reporting System (FAERS) data (Q4 2019-Q3 2024), employing disproportionality analyses (ROR, PRR, BCPNN, EBGM) and sensitivity assessments to evaluate 844 reports. Hepatic events (46.7% occurring within 30 days) and systemic reactions (fatigue, hair discoloration) dominated AE profiles, with median onset at 35 days (IQR 14-94). Sex-specific susceptibilities emerged, as females comprised 71.3% of cases and exhibited stronger signals for constipation and alopecia. Disproportionality analysis identified 84 significant Preferred Terms, while sensitivity analyses excluding confounders reinforced signal robustness. Despite therapeutic efficacy, hepatotoxicity and delayed-onset AEs (18.2% occurring after 6 months) necessitate rigorous adherence to risk mitigation protocols and long-term monitoring. These real-world data underscore sex-dimorphic AE patterns and validate FAERS as a critical tool for post-marketing surveillance, informing risk-benefit optimization in TGCT management.

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