Yang Yana, Li Linman, Tian Jing, Ma Linwen, Wu Yaoxin, Luo Qian, Luo Yan
Nursing Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Health Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Pharmacol. 2024 Nov 11;15:1453429. doi: 10.3389/fphar.2024.1453429. eCollection 2024.
Immune-related adverse events (irAEs) typically occur within 3 months of initiating immune-checkpoint inhibitors (ICIs), which has been extensively documented. But the clinical profiles of late-onset irAEs remain inadequately characterized. Therefore, this study aims to quantify the correlation between delayed irAEs and ICIs, and to delineate the profiles of delayed toxicities associated with ICIs using data from the Food and Drug Administration Adverse Event Reporting System (FAERS).
Data from the January 2011 to December 2023 in FAERS database were extracted. Four signal detection indices, reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS), were employed to evaluate the associations between ICIs and delayed irAEs.
A total of 147,854 cases were included in this study, of which 3,738 cases related to delayed irAEs were identified. Generally, 8 signals at System Organ Class (SOC) level were found to be associated with ICIs. Males had a slightly higher reporting frequencies for respiratory disorders (ROR = 0.95) and blood and lymphatic system disorders (ROR = 1.22), but lower reporting frequencies for immune system disorders (ROR = 1.16). Three monotherapy (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing gastrointestinal disorders (ROR = 1.66, 1.16, 1.99) and metabolism disorders (ROR = 2.26, 1.74, 3.13). Anti-PD-1 therapy exhibited higher rates of respiratory toxicities (ROR = 1.46 versus 0.82) and skin toxicities (ROR = 1.27 versus 0.94) compared with anti-CTLA-4 therapy. At PT levels, pneumonitis (ROR: from 11.85 to 29.27) and colitis (ROR: from 2.11 to 24.84) were the most notable PT signals associated with all three ICI regimens. For outcomes of delayed irAEs, gastrointestinal disorders showed the highest proportion (51.06%) of death.
Our pharmacovigilance analysis indicates that a small percentage of patients receiving ICIs therapy experience delayed irAEs, which are challenging to manage and may result in severe consequences. Prompt identification and intervention of these delayed irAEs are crucial in clinical practice.
免疫相关不良事件（irAEs）通常在开始使用免疫检查点抑制剂（ICIs）后的3个月内发生，这已被广泛记录。但迟发性irAEs的临床特征仍未得到充分描述。因此，本研究旨在量化迟发性irAEs与ICIs之间的相关性，并使用美国食品药品监督管理局不良事件报告系统（FAERS）的数据描绘与ICIs相关的迟发性毒性特征。
提取FAERS数据库2011年1月至2023年12月的数据。采用四个信号检测指标，即报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS），来评估ICIs与迟发性irAEs之间的关联。
本研究共纳入147,854例病例，其中识别出3738例与迟发性irAEs相关的病例。总体而言，在系统器官分类（SOC）水平发现8个信号与ICIs相关。男性呼吸系统疾病（ROR = 0.95）和血液及淋巴系统疾病（ROR = 1.22）的报告频率略高，但免疫系统疾病的报告频率较低（ROR = 1.16）。三种单药疗法（抗PD-1、抗PD-L1和抗CTLA-4）均与胃肠道疾病（ROR = 1.66、1.16、1.99）和代谢紊乱（ROR = 2.26、1.74、3.13）的显著增加相关。与抗CTLA-4疗法相比，抗PD-1疗法表现出更高的呼吸系统毒性发生率（ROR = 1.46对0.82）和皮肤毒性发生率（ROR = 1.27对0.94）。在首选术语（PT）水平，肺炎（ROR：从11.85到29.27）和结肠炎（ROR：从2.11到24.84）是与所有三种ICI治疗方案相关的最显著PT信号。对于迟发性irAEs的结局，胃肠道疾病的死亡比例最高（51.06%）。
我们的药物警戒分析表明，一小部分接受ICIs治疗的患者会经历迟发性irAEs，这些irAEs难以管理，可能导致严重后果。在临床实践中，及时识别和干预这些迟发性irAEs至关重要。
