基于FAERS数据库对免疫检查点抑制剂致噬血细胞性淋巴组织细胞增生症不良事件的风险信号挖掘

肖洒; 蔡泽政; 朱志洪; 吴肇伟; 王敏; 雷露雯

doi:10.13748/j.cnki.issn1007-7693.20250599

基于FAERS数据库对免疫检查点抑制剂致噬血细胞性淋巴组织细胞增生症不良事件的风险信号挖掘

Risk Signal Mining of Hemophagocytic Lymphohistiocytosis Adverse Events Induced by Immune Checkpoint Inhibitors Based on the FAERS Database

摘要

摘要:
目的基于美国 FDA不良事件报告系统(FDA adverse event reporting system，FAERS)，评估和比较不同免疫检查点抑制剂(immune checkpoint inhibitors，ICIs)和噬血细胞性淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis，HLH)之间的联系，以期为该类药物的安全合理使用提供警示参考。
方法收集 2004年第一季度至2024年第三季度以ICIs作为首要怀疑药物，HLH作为首选术语的病例报告。采用报告比值比(reporting odds ratio，ROR)、比例报告比(proportional reporting ratio，PRR)、贝叶斯置信传播神经网络(Bayesian confidence propagation neural network，BCPNN)和多项泊松收缩器(multi-item gamma Poisson shrinker，MGPS)算法研究 ICIs与HLH之间的关系，并进一步研究了HLH的发病时间和不良事件结局。
结果共纳入393例ICIs引发的HLH不良事件报告。男性患者(227例，57.76%)显著多于女性患者(145例，36.90%)，老年患者(≥65岁)占46.31%。阿替利珠单抗、伊匹木单抗、西米普利单抗、帕博利珠单抗、纳武利尤单抗、度伐利尤单抗均显示出HLH信号，阿替利珠单抗的信号最强。ICIs导致HLH的中位发病时间为25.00 d，其中阿替利珠单抗的中位发病时间最短(10.50 d)，而西米普利单抗最长(80.00 d)。
结论进一步完善了ICIs导致HLH发病风险及临床特征，医师应特别警惕出现ICIs 相关HLH，以保证患者治疗安全性。

Abstract:
OBJECTIVE To evaluate and compare the association between different immune checkpoint inhibitors(ICIs) and hemophagocytic lymphohistiocytosis(HLH) based on the US FDA adverse event reporting system(FAERS), so as to provide a warning reference for the safe and reasonable use of such drugs.
METHODS Case reports were collected from Q1 2004 to Q3 2024 with ICIs as the primary suspected drug and HLH as the preferred term. Reporting odds ratio(ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN) and multi-item gamma Poisson were used shrinker(MGPS) algorithm were used to study the relationship between ICIs and HLH, and further investigated the onset time and adverse event outcome of HLH.
RESULTS A total of 393 adverse events of ICIs-induced HLH were included. There were significantly more male patients(227 cases, 57.76%) than female patients(145 cases, 36.90%), and elderly patients(≥65 years old) accounted for 46.31%. Attilizumab, ipilimumab, ciiprilizumab, pabolizumab, nebuliumab and duvaliumab all showed HLH signal, and attilizumab had the strongest signal. The median onset time of HLH caused by ICIs was 25.00 d, with attilizumab having the shortest median onset time(10.50 d) and cimiplizumab the longest(80.00 d).
CONCLUSION The risk and clinical features of HLH caused by ICIs have been further improved, and physicians should be especially vigilant against the occurrence of ICIs-related HLH to ensure the safety of patients.

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