Risk analysis of regorafenib related hepatobiliary system injury based on the US Food and Drug Administration Adverse Event Reporting System
Department of Pharmacy, Chengdu Fifth People′s Hospital, Chengdu 611130, China; Department of Pharmacy, Southwest Medical University, Sichuan Province, Luzhou 646000, China
Abstract：Objective To explore the risks and influencing factors of regorafenib related hepatobiliary system injury. Methods Reports of regorafenib related hepatobiliary system adverse events received from 4th quarter, 2012 to 3rd quarter, 2018 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected. The signal intensity of hepatobiliary system adverse events related to regorafenib was screened and statistically analyzed by report odds ratio (ROR) and proportional report ratio (PRR), and their influencing factors were analyzed by logistic regression analysis. Results A total of 26-013 adverse event reports related to regorafenib were retrieved, and 28 preferred terms were screened as suspicious hepatobiliary system related adverse event signals. Results from sorting the signal intensity of adverse events using ROR, PRR and their lower limit of 95% confidence interval (CI) showed that elevation of jaundice and bilirubin had the strongest signal (ROR=8.56, 95%CI lower limit: 7.66; PRR=8.46, 95%CI lower limit: 7.58), followed by other laboratory abnormalities (ROR=6.05, 95%CI lower limit: 4.95; PRR=6.03, 95%CI lower limit: 4.94) and then liver related diseases (ROR=5.46, 95%CI lower limit: 4.71; PRR=5.43, 95%CI lower limit: 4.69). Logistic regression analysis showed that the risk of hepatobiliary system adverse events was higher when the regorafenib dose was>80~<160-mg/d, compared with the dose of ≤80-mg/d (OR=1.702, 95%CI: 1.230-2.356, P=0.001), and was lower in patients with gastrointestinal stromal tumors, compared with other tumors (OR=0.436, 95%CI: 0.240-0.792, P=0.006). Conclusion Regorafenib has the risk of hepatobiliary system injury, and a higher dose may be related to the increased risk.
龙霞，曾晓欢，干小红. 基于美国FDA不良事件报告系统数据库的瑞戈非尼肝胆系统损伤风险分析[J]. 药物不良反应杂志, 2020, 22(4): 227-232.
Long Xia, Zeng Xiaohuan, Gan Xiaohong. Risk analysis of regorafenib related hepatobiliary system injury based on the US Food and Drug Administration Adverse Event Reporting System. Adverse Drug Reactions Journal, 2020, 22(4): 227-232.
