Lutetium Lu 177 vipivotide tetraxetan不良事件信号挖掘与分析

Data Mining and Analysis of Adverse Events for Lutetium Lu 177 Vipivotide Tetraxetan

关键词:  lutetium Lu 177 vipivotide tetraxetan  不良事件  首选术语  有效信号

Key words:  lutetium Lu 177 vipivotide tetraxetan  adverse event  preferred term  effective signal

摘要:

目的 基于美国食品药品监督管理局不良事件报告系统(FAERS)，对新型放射性治疗药物lutetium Lu 177 vipivotide tetraxetan的不良事件信号进行挖掘和分析。方法 检索FAERS中2022年第2季度—2022年第4季度以lutetium Lu 177 vipivotide tetraxetan为首要怀疑的不良事件报告，分析报告特征、人口学特征及不良事件的诱发时间。采用报告比值(reporting odds ratio，ROR)法、比例报告比值比(proportional reporting ratio，PRR)法、贝叶斯置信传播神经网络(Bayesian confidence propagation neural network，BCPNN)法和多项伽马泊松分布缩减(multi-item gamma Poisson shrinker，MGPS)法挖掘有效信号。结果 共获得以lutetium Lu 177 vipivotide tetraxetan为首要怀疑药物的不良事件报告634例，报告数量整体呈逐月增长趋势，其中568例(89.6%)发生在美国。在所统计的报告中，常见年龄为61~80岁(75.4%)，体质量为61~80 kg (50.9%)。不良事件的诱发时间主要集中于0~30 d，占41.5%。基于ROR、PRR、BCPNN、MGPS 4种算法，在首选术语(preferred term，PT)层级共获得6个有效信号，分别为贫血(PT：10002034)、血小板减少症(PT：10043554)、实验室检查异常(PT：10023547)、血小板计数降低(PT：10035528)、全血细胞计数减少(PT：10017413)、口干(PT：10013781)。结论 在使用lutetium Lu 177 vipivotide tetraxetan时，应重点加强用药1个月内的临床监护，并关注全血细胞、血小板计数相关实验室检查结果。

Abstract:

BACKGROUND On March 2022, the United States Food and Drug Administration(FDA) announced the approval of radiolabeled drug lutetium Lu 177 vipivotide tetraxetan for treatment of adult patients with prostate specific membrane antigen(PSMA)-positive metastatic castration-resistant prostate cancer who have been treated with androgen-receptor pathway inhibition and taxane-based chemotherapy. As PSMA is barely expressed on non-prostatic tissue, it has a very low background accumulation in healthy tissue, consequently, avoiding severe adverse drug reaction of lutetium Lu 177 vipivotide tetraxetan. A multicenter phase Ⅲ VISION study(NCT 03511664) showed that about 30% of patients with evaluable disease at baseline demonstrated an overall response with lutetium Lu 177 vipivotide tetraxetan plus standard care, compared to only 2% in the control arm. The high efficacy and mild adverse drug reaction of lutetium Lu 177 vipivotide tetraxetan cause opportunities for the healthcare systems and represent an important next step towards novel oncotherapy, but also cause great challenges in its clinical use due to lack of practical experience. Currently, data on the large sample and real-world comprehensive safety of lutetium Lu 177 vipivotide tetraxetan are still limited. Therefore, it is necessary to employ data mining algorithms to seek out the potential adverse event signals of lutetium Lu 177 vipivotide tetraxetan by post-marketing monitoring. METHODS FDA Adverse Event Reporting System(FAERS) is a publicly available, voluntary, and spontaneous reporting database. In the present study, the adverse events reported from the second quarter of 2022 to the fourth quarter of 2022 with lutetium Lu 177 vipivotide tetraxetan from FAERS were retrospectively analyzed. Seven types of datasets, including patient demographic and administrative information(DEMO), drug information(DRUG), therapy start dates and end dates for reported drugs(THER), adverse event results(OUTC), adverse event sources(PRSP), coded for the adverse events(REAC), and indications for use/diagnosis(INDI) were used. The reports of lutetium Lu 177 vipivotide tetraxetan were identified using generic name(LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN in prod_ai column) and trade name(PLUVICTO in drug name column) in the DRUG dataset. The adverse event reports with the role_cod as the primary suspected(PS) were chose. Next, the report characteristics, demographic characteristics and onset time of lutetium Lu 177 vipivotide tetraxetan-associated adverse events were analyzed. The adverse events were coded using preferred terms(PT) derived from the standardized Medical Dictionary for Regulatory Activities 25.1(MedDRA), which contained 27 system organ classes(SOCs). Four algorithms, including reporting odds ratio(ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN) and multi-item gamma Poisson shrinker(MGPS) were used to detect the signals. All the four data mining algorithms were based on the disproportionality analysis. An adverse event signal was detected only when it conformed to all of the four algorithms criteria simultaneously. RESULTS A total of 634 reports associated with lutetium Lu 177 vipivotide tetraxetan were considered. As a whole, the number of reports had increased gradually month-on-month, and 568(89.6%) reports occurred in the United States. The most common age and body weight groups were 61-80 years(75.4%) and 61-80 kg(50.9%), respectively. Most reports occurred within 30 d after administration of lutetium Lu 177 vipivotide tetraxetan, accounting for 41.5%. Based on 4 algorithms of ROR, PRR, BCPNN and MGPS, six effective signals at the PT level were detected, including anaemia(PT: 10002034), thrombocytopenia(PT: 10043554), laboratory test abnormal(PT: 10023547), platelet count decreased(PT: 10035528), full blood count decreased(PT: 10017413) and dry mouth(PT: 10013781). CONCLUSION When using lutetium Lu 177 vipivotide tetraxetan, it is important to strengthen clinical monitoring within one month and pay attentions to laboratory results including complete blood cell and platelet count. This study might provide powerful support for clinical monitoring of lutetium Lu 177 vipivotide tetraxetan.