伊立替康脂质体不良反应特征:基于FAERS数据库的真实世界研究OA

Background and purpose:As a novel anticancer drug,liposomal irinotecan has demonstrated significant efficacy in treating gastrointestinal tumors such as metastatic pancreatic cancer.However,its safety profile requires systematic evaluation.Currently,comprehensive real-world studies on the safety of liposomal irinotecan remain incomplete.This study conducted signal mining based on the FDA Adverse Event Reporting System(FAERS)database to comprehensively analyze the occurrence characteristics and potential risks of irinotecan liposome-associated adverse events(AEs),providing safety evidence for rational clinical use.Methods:Adverse event reports related to irinotecan liposome were extracted from the FAERS database from the first quarter of 2004 to the third quarter of 2024.After deduplicating the data,four algorithms:report odds ratio(ROR),proportional reporting ratio(PRR),Bayesian confidence propagation neural network(BCPNN),and empirical Bayesian geometric mean(EBGM),were employed for signal detection to analyze AE occurrence in the real world.This article is exempt from ethical review.Results:A total of 1 185 AE signals were detected,involving 25 system organ classes(SOCs).The AEs were primarily concentrated in gastrointestinal disorders(19.7%,ROR=2.69),blood and lymphatic system disorders(7.2%,ROR=4.65),and hepatobiliary disorders(2.0%,ROR=2.48).High-frequency preferred terms(PTs)included diarrhea(17.0%),neutropenia(7.3%),and off-label use(25.5%).Events with high signal intensity were most prominent for infective cholangitis(ROR=384.03),migrans thrombophlebitis(ROR=141.33),and duodenal stenosis(ROR=137.70).This study also identified unexpected signals,including hepatobiliary toxicity(cholangitis,liver abscess),thrombotic events(vena cava thrombosis,portal vein thrombosis),infectious complications(enterocolitis,proteus infection,clostridial infection),immune system reactions(anaphylactoid reaction),and nervous system disorders(peripheral sensorimotor neuropathy,peripheral sensory neuropathy).Time analysis revealed that 47.61%of AEs occurred within 30 days post-treatment(median time:35 days).Conclusion:The real-world safety data of irinotecan liposomes not only verified the adverse reactions known in the instructions,but also revealed multiple new potential risk signals including hepatobiliary toxicity,thrombotic events and specific infections.It is recommended to strengthen pharmacovigilance in clinical practice,with a focus on high-frequency,newly identified,and severe adverse reactions.Individualized treatment adjustments based on the characteristics of drug-related adverse reactions should be implemented to enhance medication safety.