Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
School of Pharmacy, Capital Medical University, Beijing, China.
Cancer Med. 2023 Apr;12(8):9167-9174. doi: 10.1002/cam4.5655. Epub 2023 Feb 3.
BACKGROUND: Hepatic failure induced by immune checkpoint inhibitors (ICIs) has been reported in only a few case series and case reports. OBJECTIVE: We aimed to explore the association between ICIs and hepatic failure and characterize the clinical features of ICI-associated hepatic failure in the pharmacovigilance database. METHODS: Data from the first quarter (Q1) of 2015 to the fourth quarter (Q4) of 2021 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved for disproportionality and Bayesian analysis. Reporting odds ratios (ROR) and information component (IC) were used to evaluate correlations between ICIs and hepatic failure. RESULTS: Hepatic failure occurred in 0.19% (18,454/9,647,655) of all cases in the FAERS database, of which 654 cases were associated with ICIs. The overall median time from ICIs initiation to hepatic failure onset was 38 days, 72.3% of the adverse events occurred within the first 3 months, and 68.65% of the cases died after developing hepatic failure. In general, a strong signal was shown between ICIs and hepatic failure (ROR = 2.70, IC = 1.39). For the three categories of ICIs, programmed cell death 1 ligand 1 inhibitors (ROR = 3.09, IC = 1.57) had a higher risk signal than programmed cell death protein 1 inhibitors and cytotoxic T lymphocyte-associated protein 4 inhibitors. For monotherapy, atezolizumab showed the strongest risk signal (ROR = 4.07, IC = 1.90). The combination of nivolumab and ipilimumab showed stronger signals of hepatic failure compared with nivolumab or ipilimumab alone (nivolumab + ipilimumab vs. ipilimumab: ROR = 1.40, IC = 0.16; nivolumab + ipilimumab vs. nivolumab: ROR = 1.24, IC = 0.34). Considering the concomitant agents used with ICIs, the majority of these regimens showed stronger signals than ICI monotherapy, such as acetaminophen (ICIs + acetaminophen vs. ICIs: ROR = 1.06, IC = 0.32). CONCLUSIONS: ICIs had possible strong signals associated with hepatic failure, and most cases of hepatic failure occurred within the first 3 months and had poor outcomes, which should attract clinical attention.
背景：免疫检查点抑制剂（ICI）引起的肝衰竭仅在少数病例系列和病例报告中报道过。
目的：我们旨在探讨 ICI 与肝衰竭之间的关联，并在药物警戒数据库中描述与 ICI 相关的肝衰竭的临床特征。
方法：检索美国食品和药物管理局不良事件报告系统（FAERS）数据库 2015 年第一季度（Q1）至 2021 年第四季度（Q4）的数据，进行不相称性和贝叶斯分析。报告比值比（ROR）和信息成分（IC）用于评估 ICI 与肝衰竭之间的相关性。
结果：在 FAERS 数据库中，所有病例的肝衰竭发生率为 0.19%（18,454/9,647,655），其中 654 例与 ICI 相关。ICI 引发肝衰竭的中位时间为 38 天，72.3%的不良事件发生在最初 3 个月内，68.65%的病例在发生肝衰竭后死亡。总体而言，ICI 与肝衰竭之间存在强烈信号（ROR=2.70，IC=1.39）。对于三种 ICI 类别，细胞程序性死亡配体 1 抑制剂（ROR=3.09，IC=1.57）的风险信号高于细胞程序性死亡蛋白 1 抑制剂和细胞毒性 T 淋巴细胞相关蛋白 4 抑制剂。对于单药治疗，阿特珠单抗显示出最强的风险信号（ROR=4.07，IC=1.90）。与单独使用纳武单抗或伊匹单抗相比，纳武单抗联合伊匹单抗显示出更强的肝衰竭信号（纳武单抗+伊匹单抗与伊匹单抗：ROR=1.40，IC=0.16；纳武单抗+伊匹单抗与纳武单抗：ROR=1.24，IC=0.34）。考虑到与 ICI 联合使用的伴随药物，这些方案中的大多数与 ICI 单药治疗相比显示出更强的信号，例如对乙酰氨基酚（ICI+对乙酰氨基酚与 ICI：ROR=1.06，IC=0.32）。
结论：ICI 与肝衰竭之间可能存在强烈信号，大多数肝衰竭病例发生在最初 3 个月内，且预后不良，这应引起临床关注。
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