Cardiovascular Adverse Events of JAK vs. TNF Inhibitors using the Korean Pharmacovigilance Database

Introduction Janus kinase inhibitors (JAK-Is), as novel medications, are utilized in treating immune-mediated inflammatory diseases such as rheumatoid arthritis. However, concerns about their cardiovascular safety associated with the use of JAK inhibitors have been increasing in recent years. This study aimed to compare the risk of cardiovascular events (CVEs) in patients taking JAK-Is and tumor necrosis factor alpha inhibitors (TNF-Is) using the Korea Adverse Event Reporting System (KAERS) database. Methods Adverse event (AE) reports between January 1, 2015 and December 31, 2020 of JAK-Is (tofacitinib or baricitinib) or TNF-Is (adalimumab, etanercept, or golimumab) were included. CVEs were categorized into major cardiovascular events (MACEs), thrombosis, and other CVEs. The reporting odds ratios (RORs) for outcomes with 95% confidence interval (CIs) were calculated using 2x2 contingency tables. Results A total of 625 AE reports were identified for JAK-I and 4,777 for TNF-Is, resulting in 876 and 7,999 drug-AE pairs, respectively. Disproportionality analysis showed reporting signals suggesting possible associations between JAK-Is and CVEs compared with TNF-Is (ROR: 4.90, 95% CI: 2.80-8.59), with particularly pronounced for thrombosis (ROR: 12.70, 95% CI: 5.10-31.66). These trends were particularly notable in women (CVEs: ROR: 7.52, 95% CI: 3.06-18.47) and in patients over 50 years old (CVEs: ROR: 5.01, 95% CI: 2.02-12.43). Conclusion This disproportionality analysis using a national pharmacovigilance database identified reporting signals for total CVEs with JAK-Is compared to TNF-Is; in particular, a significant signal for thrombosis was observed.