Study on the risk of cholangitis induced by immune checkpoint inhibitors based on the US FDA Adverse Event Reporting System
10.3760/cma.j.cn114015-20220207-00099
- VernacularTitle:基于美国FDA不良事件报告系统数据库的免疫检查点抑制剂致胆管炎风险分析
- Author:
Yanyan ZHAO
1
;
Huixian ZHANG
;
Luhua MENG
;
Jianbo FENG
Author Information
1. 济宁医学院附属医院药剂科，济宁 272029
- Publication Type:Journal Article
- Keywords:
Antineoplastic agents;
Immune checkpoint inhibitors;
Cholangitis;
Drug-related side effects and adverse reactions
- From:
Adverse Drug Reactions Journal
2022;24(8):424-428
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the risk of cholangitis induced by different immune checkpoint inhibitors (ICIs).Methods:Through the OpenVigil data platform, adverse event (AE) reports related to nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, ipilimumab, and tremelimumab from the first quarter of 2011 to the third quarter of 2021 in the US FDA Adverse Event Reporting System (FAERS) database were collected. Risk signal mining for cholangitis was performed using reported odds ratio ( ROR) method. The detection threshold of the risk signal was set as that the number of AE reports was greater than or equal to 3 and the lower limit of the 95% confidence interval ( CI) of the ROR was greater than 1. The higher the ROR and its 95 %CI lower limit, the stronger the signal intensity. The intensity of the risk signal of cholangitis due to different ICIs was compared and the main characteristics (sex, age, type of primary tumor, time of occurrence of AE, and outcome) of patients with ICIs-related cholangitis were analyzed descriptively. Results:A total of 52 440 AE reports related to the above 8 ICIs were collected, of which 410 cases were about cholangitis. The drugs that were detected with positive risk signals were nivolumab, pembrolizumab, atezolizumab, durvalumab monotherapy, and ipilimumab combined with nivolumab. Their number of AE reports were 213, 107, 48, 5, and 29 (402 patients in total), and the corresponding ROR (lower limit of 95 %CI) were 37.88 (32.89), 26.07 (21.46), 32.12 (24.10), 13.63 (5.65), and 14.46 (10.02), respectively. The risk signal intensity was nivolumab, atezolizumab, pembrolizumab, ipilimumab combined with nivolumab, and durvalumab in order. Seeing from the available data among the reports, males were more than females (233∶110=2.1∶1), 55.2% (222/402) of patients were 65 years old and over, and 48.0% (193/402) of patients were non-small cell lung cancer. ICIs-related cholangitis could result in hospitalization or prolongation of hospitalization in 42.3% (170/402), requiring emergency treatment in 40.0% (161/402), life-threatening in 2.0% (8/402), and death in 15.7% (63/402) of patients. Conclusions:The risk of cholangitis induced by ICIs is different and the risk signal of nivolumab is the strongest. Cholangitis is a serious AE of ICI, which should attract clinical attention.
