PDF(Pubmed)
Abstract：
Background: Several poly ADP ribose polymerase inhibitors (PARPis) are currently approved for the treatment of a variety of cancers. The safety profile of PARPis has not yet been systemically analyzed in the real world. We conducted this pharmacovigilance analysis using the US FDA\'s Adverse Event Reporting System (FAERS) database to explore the difference in adverse events (AEs) among PARPis. Methods: FAERS data (December 2014 to October 2021) were searched for reports of all FDA-approved PARPis across all indications. We used the standardized MedDRA query (SMQ) generalized search AEs on the preferred term (PT) level based on case reports. After filtering duplicate reports, disproportionality analysis was used to detect safety signals by calculating reporting odds ratios (ROR). Reports were considered statistically significant if the 95% confidence interval did not contain the null value. Results: Within the standardized MedDRA queries, significant safety signals were found, including those for olaparib [blood premalignant disorders (ROR = 17.06)], rucaparib [taste and smell disorders (ROR = 9.17)], niraparib [hematopoietic throbocytopenia (ROR = 28.2)], and talazoparib [hematopoietic erythropenia (ROR = 9.38)]. For AEs on the PT level, we found several significant signals, including platelet count decreased with niraparib (ROR = 52.78); red blood cell count decreased with niraparib (ROR = 70.47) and rucaparib (ROR = 15.09); myelodysplastic syndrome with olaparib (ROR = 35.47); acute myeloid leukaemia with olaparib (ROR = 25.14); blood pressure fluctuation with niraparib (ROR = 20.54); lymphangioleiomyomatosis with niraparib (ROR = 471.20); photosensitivity reaction with niraparib (ROR = 21.77) and rucaparib (ROR = 18.92); renal impairment with rucaparib (ROR = 33.32); and interstitial lung disease with Olaparib (ROR = 11.31). All the detected safety signals were confirmed using signals of disproportionality reporting methods. Conclusion: PARPis differed in their safety profile reports. The analysis of the FAERS database revealed significant safety signals that matched previously published case reports, including serious gastrointestinal, blood and lymphatic system, cardiovascular and respiratory complications, which require individualized drug administration according to patients\' conditions.
摘要：
背景：几种聚ADP核糖聚合酶抑制剂（PARPis）目前已被批准用于治疗多种癌症。PARPis的安全性尚未在现实世界中进行系统分析。我们使用美国FDA的不良事件报告系统（FAERS）数据库进行了药物警戒分析，以探讨PARPis之间不良事件（AE）的差异。方法：搜索FAERS数据（2014年12月至2021年10月），查找所有适应症中所有FDA批准的PARPis的报告。我们使用基于病例报告的首选术语（PT）水平的标准化MedDRA查询（SMQ）广义搜索AE。过滤重复报告后，不相称性分析用于通过计算报告比值比(ROR)来检测安全性信号。如果95％置信区间不包含空值，则报告被认为具有统计学意义。结果：在标准化的MedDRA查询中，发现了重要的安全信号，包括奥拉帕尼[血液癌前病变（ROR=17.06）]，rucaparib[味觉和嗅觉障碍（ROR=9.17）]，尼拉帕尼[造血红细胞减少症（ROR=28.2）]，和talazoparib[造血红细胞减少症（ROR=9.38）]。对于PT级别的AE,我们发现了几个重要的信号,包括尼拉帕尼组血小板计数降低（ROR=52.78）；尼拉帕尼组红细胞计数降低（ROR=70.47）和鲁卡帕尼组降低（ROR=15.09）；奥拉帕尼组骨髓增生异常综合征（ROR=35.47）；奥拉帕尼组急性髓系白血病（ROR=25.14）；血压波动与尼拉帕利（ROrnalaparib=所有检测到的安全性信号均使用不相称性报告方法确认。结论：PARPis的安全性报告不同。对FAERS数据库的分析显示了与先前发布的病例报告相匹配的重要安全信号，包括严重的胃肠道，血液和淋巴系统，心血管和呼吸系统并发症，这需要根据患者的情况进行个体化的药物管理。
