Abstract：
Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI-induced CLS through a systematic review and to assess a potential safety signal.
Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0.
A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8).
This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.
Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0.
A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8).
This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.
摘要：
背景：尽管少数病例报告表明免疫检查点抑制剂（ICIs）是毛细血管渗漏综合征（CLS）的潜在诱导剂，不能排除偶然发现。这项研究的目的是通过系统评价来描述ICI诱导的CLS的临床特征，并评估潜在的安全性信号。
方法：Medline/PubMed，Embase,并对每周反应进行了筛选，在2023年1月15日之前,我们使用世界卫生组织药物警戒数据库进行了一项全球不成比例性研究.不成比例报告的信号被定义为具有超过0的95％可信度区间（CrI）下边界的贝叶斯信息成分（IC）。
结果：共纳入47例ICI相关CLS，14来自系统评价（61篇筛选文章），33来自VigiBase（34,058,481份药物不良反应报告）。从ICI开始到CLS发作的中位时间为12周（四分位距8-49，n=24）。总共57％（8/14）的患者在CLS之前经历了免疫相关的不良事件（irAE）。23%(7/31)的患者报告了致命的结果。与所有其他药物相比，ICIs的CLS报告显着（IC2.4，95％CrI从1.8到2.8）。
结论：这项研究显示了ICI诱导的CLS的不相称性报告的重要信号，其特点是发病时间长，与该病的特发性形式相比，其发作不那么突然，血液浓缩模式不那么一致。
方法：Medline/PubMed，Embase,并对每周反应进行了筛选，在2023年1月15日之前,我们使用世界卫生组织药物警戒数据库进行了一项全球不成比例性研究.不成比例报告的信号被定义为具有超过0的95％可信度区间（CrI）下边界的贝叶斯信息成分（IC）。
结果：共纳入47例ICI相关CLS，14来自系统评价（61篇筛选文章），33来自VigiBase（34,058,481份药物不良反应报告）。从ICI开始到CLS发作的中位时间为12周（四分位距8-49，n=24）。总共57％（8/14）的患者在CLS之前经历了免疫相关的不良事件（irAE）。23%(7/31)的患者报告了致命的结果。与所有其他药物相比，ICIs的CLS报告显着（IC2.4，95％CrI从1.8到2.8）。
结论：这项研究显示了ICI诱导的CLS的不相称性报告的重要信号，其特点是发病时间长，与该病的特发性形式相比，其发作不那么突然，血液浓缩模式不那么一致。
