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

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-Is 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 (2204A0025).

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, thrombosis, and other CVEs. The reporting odds ratios (RORs) for outcomes with 95% confidence intervals (CIs) were calculated using 2 × 2 contingency tables.

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 for CVEs in women (ROR: 7.52, 95% CI: 3.06-18.47) and in patients over 50 years old (ROR: 5.01, 95% CI: 2.02-12.43).

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.