School of Medicine, Tongji University Shanghai, China.
Department of Health Statistics, Naval Medical University, Shanghai, China.
Br J Clin Pharmacol. 2022 Sep;88(9):4180-4190. doi: 10.1111/bcp.15361. Epub 2022 May 2.
As a new type of drug developed rapidly in recent years, Janus kinase inhibitors (JAKinibs) have caused controversy due to possible adverse reactions of thromboembolism. The aim of this study was to analyse and evaluate the association between thromboembolic events and the use of JAKinibs, on the base of the latest data in the Food and Drug Administration's Adverse Event Reporting System.
A disproportionality analysis was conducted, utilizing data from 1 January 2012 to 30 September 2021 in the FAERS. For each drug-adverse event pair, reporting odds ratio (ROR) and information components (IC) were calculated.
A total of 15 positive safety signals were detected within the FAERS: ruxolitinib was significantly associated with portal vein thrombosis (ROR = 3.49, IC = 1.50); tofacitinib immediate release with pulmonary embolism (ROR = 2.09, IC = 1.02) and thrombosis (ROR = 1.15, IC = 0.18); tofacitinib extended release with pulmonary embolism (ROR = 1.27, IC = 0.26) and thrombosis (ROR = 1.29, IC = 0.33); baricitinib with deep vein thrombosis (ROR = 8.27, IC = 3.00), portal vein thrombosis (ROR = 1.97, IC = 0.63), pulmonary embolism (ROR = 7.90, IC = 2.94), thrombosis (ROR = 2.04, IC = 0.93) and venous thrombosis (ROR = 2.15, IC = 0.81); upadacitinib with pulmonary embolism (ROR = 1.25, IC = 0.25), pulmonary thrombosis (ROR = 5.32, IC = 2.33) and thrombosis (ROR = 2.72, IC = 1.39); and filgotinib with pulmonary embolism (ROR = 4.83, IC = 2.10). In the analysis of the time to onset of thromboembolic events, no obviously recognizable pattern was found. Several safety signals with embolic and thrombotic events (Standardised MedDRA Query) were found in the study.
This pharmacovigilance study covered 8 types of JAKinib that are already on the market, and provided new safety signals based on past safety information. Some of these signals still need more medical evidence.
作为近年来迅速发展的新型药物，Janus 激酶抑制剂（JAKinibs）由于可能发生血栓栓塞的不良反应而引起争议。本研究旨在根据食品和药物管理局不良事件报告系统中的最新数据，分析和评估血栓栓塞事件与 JAKinibs 使用之间的关联。
利用 FAERS 中 2012 年 1 月 1 日至 2021 年 9 月 30 日的数据，进行了不相称性分析。对于每对药物-不良事件，计算报告比值比（ROR）和信息成分（IC）。
在 FAERS 中总共检测到 15 个阳性安全信号：鲁索替尼与门静脉血栓形成显著相关（ROR=3.49，IC=1.50）；托法替尼速释与肺栓塞（ROR=2.09，IC=1.02）和血栓形成（ROR=1.15，IC=0.18）；托法替尼缓释与肺栓塞（ROR=1.27，IC=0.26）和血栓形成（ROR=1.29，IC=0.33）；巴利昔替尼与深静脉血栓形成（ROR=8.27，IC=3.00）、门静脉血栓形成（ROR=1.97，IC=0.63）、肺栓塞（ROR=7.90，IC=2.94）、血栓形成（ROR=2.04，IC=0.93）和静脉血栓形成（ROR=2.15，IC=0.81）；阿布昔替尼与肺栓塞（ROR=1.25，IC=0.25）、肺血栓形成（ROR=5.32，IC=2.33）和血栓形成（ROR=2.72，IC=1.39）；和菲戈替尼与肺栓塞（ROR=4.83，IC=2.10）。在对血栓栓塞事件发生时间的分析中，没有发现明显可识别的模式。在这项研究中还发现了几个与栓塞和血栓事件（标准 MedDRA 查询）相关的安全信号。
本项药物警戒研究涵盖了 8 种已上市的 JAKinib，根据过去的安全信息提供了新的安全信号。其中一些信号仍需要更多的医学证据。
