基于FAERS数据库对ALK抑制剂相关眼部不良事件信号的挖掘与分析

Mining and analysis for ocular adverse event signals induced by ALK inhibitors based on FAERS database

目的挖掘并分析不同间变性淋巴瘤激酶(ALK)抑制剂相关的眼部不良事件(ADE),为临床安全用药提供参考。方法下载美国食品药品管理局不良事件报告系统(FAERS)数据库2011年第3季度至2024年第1季度数据,提取ALK抑制剂相关眼部ADE报告,采用报告比值比(ROR)法和信息成分(IC)法进行信号检测。统计眼部ADE的中位发生时间,并使用Weibull分布分析ALK抑制剂使用与眼部ADE发生的时间间隔关系。结果共收集到ALK抑制剂相关眼部ADE报告1575份,其中克唑替尼、塞瑞替尼、阿来替尼、布格替尼和洛拉替尼相关眼部ADE报告分别为1107、50、158、110、150份。女性患者占比更高(46.29%),年龄主要分布在18~<65岁(35.17%)。塞瑞替尼未检测到风险信号,克唑替尼、阿来替尼、布格替尼和洛拉替尼共检出13个阳性信号,克唑替尼致眼部ADE报告数量和阳性信号数位列第一,克唑替尼致闪光幻觉的信号强度最高[ROR=43.46,95%CI(36.38,51.91);IC=5.18,95%CI(4.89,5.40)]。大部分眼部ADE中位发生时间在开始用药1个月内,ALK抑制剂致失明的中位发生时间最长,为154.00(114.50,225.50)d。视觉损害、视物模糊、闪光幻觉、玻璃体飞蛾症、复视常发生在用药早期,畏光、视野缺损及失明的发生时间随机,不随用药时间变化而变化。结论不同ALK抑制剂致眼部ADE的风险有所差异,多发生于治疗早期,临床应用时应及时识别并处理ALK抑制剂的眼部ADE。

Objective To provide references for clinical safe medication by mining and analyzing signals of ocular adverse events(ADE)related to anaplastic lymphoma kinase(ALK)inhibitors.Methods The data from the third quarter in 2011 to the first quarter in 2024 were downloaded from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS),ocular ADEs associated with ALK inhibitors reports were extracted.The suspicious risk signals were mined and analyzed by reporting odds ratio(ROR)and information component(IC)method.The median occurrence time of ocular ADE was analyzed,and Weibull shape parameter test was used to analyze the relationship between ADE occurrence time and ALK inhibitor treatment time.Results A total of 1575 reports of ALK inhibitor-related ocular ADEs were collected,including 1107 reports for crizotinib,50 reports for ceritinib,158 reports for alectinib,110 reports for brigatinib and 150 reports for lorlatinib.The proportion of female patients was higher(46.29%),and the main age distribution was between 18 and less than 65 years old(35.17%).No risk signal was detected for ceritinib.13 ADE signals were obtained for crizotinib,alectinib,brigatinib and lorlatinib.Crizotinib ranked first in the number of ADE reports and positive signals,and the signal intensity of crizotinib-induced photopsia was the highest(ROR=43.46,95%CI 36.38 to 51.91;IC=5.18,95%CI 4.89 to 5.40).The median time to onset of most ocular ADEs was within one month of medication initiation,and the median time to onset of blindness caused by ALK inhibitors was the longest at 154.00(114.50,225.50)days.The visual impairment,vision blurred,photopsia,vitreous floatres and diplopia often occurred in the early stage of medication.The photophobia,visual field defect and blindness occurred randomly and did not change with treatment time.Conclusion The risk of ocular ADEs was different in different ALK inhibitors,most of which occurred in the early stage of the treatment.The ocular toxicity of ALK inhibitors should be recognized and treated in time for clinical application.