PDF(Pubmed)
Abstract：
Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack of relevant reports on adverse reaction data mining for fulvestrant. To perform data mining on adverse events (AEs) associated with fulvestrant and explore the risk factors contributing to severe AEs, providing a reference for the rational use of fulvestrant in clinical practice. Retrieved adverse event report information associated with fulvestrant from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the period from market introduction to September 30, 2023. Suspicious AEs were screened using the reporting odds ratio (ROR) and proportional reporting ratio methods based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe AEs to explore the risk factors associated with fulvestrant-induced severe AEs. A total of 6947 reports related to AEs associated with fulvestrant were obtained, including 5924 reports of severe AEs and 1023 reports of non-severe AEs. Using the disproportionality analysis method, a total of 210 valid AEs were identified for fulvestrant, with 45 AEs (21.43%) not listed in the product labeling, involving 11 systems and organs. The AEs associated with fulvestrant were sorted by frequency of occurrence, with neutropenia (325 cases) having the highest number of reports. By signal strength, injection site pruritus showed the strongest signal (ROR = 658.43). The results of the logistic regression analysis showed that concurrent use of medications with extremely high protein binding (≥ 98%) is an independent risk factor for severe AEs associated with fulvestrant. Age served as a protective factor for fulvestrant-related AEs. The co-administration of fulvestrant with CYP3A4 enzyme inhibitors did not show statistically significant correlation with the occurrence of severe AEs. Co-administration of drugs with extremely high protein binding (≥ 98%) may increase the risk of severe adverse reactions of fulvestrant. Meanwhile, age (60-74 years) may reduce the risk of severe AEs of fulvestrant. However, further clinical research is still needed to explore and verify whether there is interaction between fulvestrant and drugs with high protein binding through more clinical studies.
摘要：
Fulvestrant,作为第一个选择性雌激素受体降解剂，广泛应用于乳腺癌的内分泌治疗。然而,在现实世界中,目前缺乏氟维司群不良反应数据挖掘的相关报道。对与氟维司群相关的不良事件（AE）进行数据挖掘，并探讨导致严重AE的危险因素。为临床合理使用氟维司群提供参考。从美国食品和药物管理局（FDA）不良事件报告系统（FAERS）数据库中检索到与氟维司群相关的不良事件报告信息，涵盖从市场引入到2023年9月30日的时期。使用基于不成比例分析的报告比值比(ROR)和比例报告比方法筛选可疑AE。对重度AE进行单因素和多因素logistic回归分析，探讨氟维司群严重AE的相关危险因素。共获得6947份与氟维司群相关的不良事件报告，包括5924例严重AE报告和1023例非严重AE报告。使用不成比例分析方法，总共为氟维司群确定了210个有效的AE，产品标签中未列出45个不良事件（21.43%），涉及11个系统和器官。与氟维司群相关的AE按发生频率排序，中性粒细胞减少症（325例）的报告数量最多。根据信号强度，注射部位瘙痒信号最强(ROR=658.43)。逻辑回归分析结果显示，同时使用具有极高蛋白结合（≥98％）的药物是与氟维司群相关的严重AE的独立危险因素。年龄是氟维司群相关不良事件的保护因素。氟维司群与CYP3A4酶抑制剂的共同给药与严重AE的发生没有统计学上的显着相关性。共同施用具有极高蛋白质结合（≥98％）的药物可能会增加氟维司群严重不良反应的风险。同时,年龄（60-74岁）可降低氟维司群严重AE的风险。然而,还需要进一步的临床研究来探索和验证氟维司群与高蛋白结合药物之间是否存在相互作用。
