Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Int Immunopharmacol. 2021 Jun;95:107498. doi: 10.1016/j.intimp.2021.107498. Epub 2021 Mar 13.
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.
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.
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.
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.
免疫检查点抑制剂（ICI）治疗的患者报告了免疫相关不良事件（irAE）。然而，随着免疫相关不良事件（irAE）的数量不断增加，每种免疫检查点抑制剂方案的差异尚未得到充分评估。
利用食品和药物管理局不良事件报告系统（FAERS）从 2004 年 1 月至 2019 年 12 月的数据挖掘免疫检查点抑制剂治疗后疑似不良事件的不适当性分析。进一步评估 ICI 相关 irAE 的发病时间和病死率。
共收集到 32441 例 ICI 相关 irAE 报告。本研究表明，所有 ICI 方案均产生了肺毒性和内分泌毒性信号。结肠炎、肺炎和间质性肺病是最常见的 ICI 相关 irAE。5 种方案，包括 durvalumab 单药治疗、ipilimumab 单药治疗、ipilimumab 加 nivolumab、ipilimumab 加 pembrolizumab、durvalumab 加 tremelimumab，与 irAE 相关。抗 PD-1 药物比抗 PD-L1 药物产生更多的眼部毒性信号，而抗 PD-L1 药物报告了更多的血液学毒性信号。与抗 PD-1 或抗 PD-L1 药物相比，抗 CTLA-4 药物显示出更多的胃肠道毒性信号。durvalumab 单药治疗的肺毒性病死率最高，avelumab 单药治疗的血液学毒性病死率最高，cemiplimab 单药治疗的肾毒性和皮肤毒性病死率最高。
我们的结果表明，每种 ICI 方案都有不同的 irAE 特征。pembrolizumab 的病死率最高。ipilimumab 加 pembrolizumab 的 irAE 发病中位时间最短。预计需要进一步研究以评估 ICIs 之间是否存在临床相关差异。
