Thromboembolic events in Janus kinase inhibitors: A pharmacovigilance study from 2012 to 2021 based on the Food and Drug Administration's Adverse Event Reporting System
Ziwei Dong, Xiaofei Ye, Chenxin Chen, Rui Wang, Dongxu Liu, Xiao Xu, Xiang Zhou, Jia He
Abstract
Aims 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. Methods 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. Results A total of 15 positive safety signals were detected within the FAERS: ruxolitinib was significantly associated with portal vein thrombosis (ROR 025 = 3.49, IC 025 = 1.50); tofacitinib immediate release with pulmonary embolism (ROR 025 = 2.09, IC 025 = 1.02) and thrombosis (ROR 025 = 1.15, IC 025 = 0.18); tofacitinib extended release with pulmonary embolism (ROR 025 = 1.27, IC 025 = 0.26) and thrombosis (ROR 025 = 1.29, IC 025 = 0.33); baricitinib with deep vein thrombosis (ROR 025 = 8.27, IC 025 = 3.00), portal vein thrombosis (ROR 025 = 1.97, IC 025 = 0.63), pulmonary embolism (ROR 025 = 7.90, IC 025 = 2.94), thrombosis (ROR 025 = 2.04, IC 025 = 0.93) and venous thrombosis (ROR 025 = 2.15, IC 025 = 0.81); upadacitinib with pulmonary embolism (ROR 025 = 1.25, IC 025 = 0.25), pulmonary thrombosis (ROR 025 = 5.32, IC 025 = 2.33) and thrombosis (ROR 025 = 2.72, IC 025 = 1.39); and filgotinib with pulmonary embolism (ROR 025 = 4.83, IC 025 = 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. Conclusion 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.