Immune-related adverse events associated with immune checkpoint inhibitors: An updated comprehensive disproportionality analysis of the FDA adverse event reporting system
Immune-related adverse events associated with immune checkpoint inhibitors: An updated comprehensive disproportionality analysis of the FDA adverse event reporting system
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DOI：
10.1016/j.intimp.2021.107498
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发表时间：
2021-03-13
影响因子：
5.6
通讯作者：
Xu, Ting
中科院分区：
文献类型：
--
作者：
Chen, Chen;Wu, Bin;Xu, Ting
背景：在接受免疫检查点抑制剂(ICIS)治疗的患者中，有免疫相关不良事件的报道。然而，随着免疫相关不良事件(IrAEs)的增多，各种免疫检查点抑制方案的差异还没有得到充分的评估。方法：根据美国食品药品监督管理局不良事件报告系统(FAERS)，对2004-01/2019年12月ICIS用药后疑似不良事件进行非比例分析。进一步评估ICI相关irAEs的发病时间和病死率。结果：共收集到32,441例ICI相关irAEs的报告。这项研究表明，所有ICI方案都会产生肺毒性和内分泌毒性信号。结肠炎、肺炎和间质性肺疾病是最常见的ICI相关irAEs。与irAEs相关的有5种方案，分别为单用杜伐单抗、单抗单药、单抗+尼伏单抗、单抗+培溴利单抗、单抗+雷米诺单抗。抗PD-1药物比抗PD-L1药物产生更多的眼毒性信号，而抗PD-L1药物报告更多的血液毒性信号。与抗PD-1或抗PD-L1药物相比，抗CTLA-4药物显示更多的胃肠道毒性信号。肺毒性、血液学毒性、肾毒性和皮肤毒性在单用杜伐单抗、阿维鲁单抗、西米利单抗治疗中致死率最高。结论：不同的ICI方案具有不同的irAEs特征。培溴利珠单抗的病死率最高。Ipilimumab+pembrolizumab的irAEs的中位发病时间最短。进一步的研究有望评估ICIS之间是否存在临床上相关的差异。
Backgrounds: Immune-related adverse events were reported in patients treated with immune checkpoint inhibitors (ICIs). However, with the increasing number of immune-related adverse events (irAEs), the differences of each immune checkpoint inhibitor regimen had not been fully assessed. Methods: Disproportionality analysis was used in data mining of the suspected adverse events after ICIs administration based on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019. The onset time and fatality proportion of ICI-associated irAEs were further evaluated. Results: A total of 32,441 reports of ICI-associated irAEs were gathered. This study showed that all ICI regimens generated lung toxicity and endocrine toxicity signals. Colitis, pneumonitis and interstitial lung disease were the most common ICI-associated irAEs. Five regimens including durvalumab monotherapy, ipilimumab monotherapy, ipilimumab plus nivolumab, ipilimumab plus pembrolizumab, durvalumab plus tremelimumab were associated with irAEs. Anti-PD-1 agents generated more signals of ocular toxicities than anti-PD-L1 agents, while anti-PD-L1 agents reported more signals of hematologic toxicities. Anti-CTLA-4 agents showed more signals of gastrointestinal toxicities compared with anti-PD-1 or anti-PD-L1 agents. The highest fatality proportion of lung toxicities with durvalumab monotherapy, hematological toxicities with avelumab monotherapy, renal and skin toxicities with cemiplimab monotherapy were found. Conclusion: Our results demonstrated that each ICI regimen had different characteristics of irAEs. Pembrolizumab had the highest fatality proportion. Ipilimumab plus pembrolizumab had the shortest median time to onset irAEs. Further studies were expected to assess whether there were clinically relevant differences exist among ICIs.