JAK Inhibitors Show Comparable Cardiovascular Safety to TNF Inhibitors in Patients With RA
A large, multinational study found no increased risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKs) compared to tumor necrosis factor inhibitors (TNFi). The findings provide reassurance to clinicians evaluating cardiovascular safety in RA treatment decisions, particularly in the context of real-world populations.
The findings, published in Arthritis & Rheumatology, came from analysis of the "JAK-pot" collaboration.
The study assessed 73,008 treatment courses from 51,233 patients with RA across 15 registries, focusing on incident MACE during treatment with JAKs, TNFis, and biologic disease-modifying antirheumatic drugs (bDMARDs) with other modes of action (bDMARD-OMAs). MACE incidence was evaluated through 2 complementary approaches: a within-registry meta-analysis and a combined individual-level analysis using adjusted linear mixed Poisson regression.
During a median follow-up of 1.3 years, the overall incidence rates of MACE were 7.0 per 1,000 person-years for JAKs, 7.6 for TNFis, and 11.8 for bDMARD-OMAs. Compared with TNFis, JAKs demonstrated a similar risk profile for MACE, with a within-registry adjusted incidence rate ratio (IRR) of 0.89 (95% CI 0.63–1.25). In contrast, bDMARD-OMAs were associated with a significantly higher MACE incidence (adjusted IRR 1.35, 95% CI 1.10–1.66).
"Observational data from the JAK-pot collaboration show no evidence of an increase in cardiovascular events during the first 2 years of use with JAKi compared to TNFi in the general RA population," the authors reported.
The consistency of results between both analytical approaches strengthens the reliability of the findings. Notably, most follow-up was concentrated within the first 2 years of treatment, highlighting the relevance of early cardiovascular outcomes during treatment initiation.
This findings of the study support the continued use of JAKs as a viable option in RA management, without heightened short-term cardiovascular risk relative to TNFis. These results are particularly timely in light of ongoing scrutiny surrounding the safety profiles of JAK inhibitors.
The authors emphasized that while the findings apply to the general RA population, ongoing surveillance remains important, particularly in patients with established cardiovascular risk factors.
Reference
Aymon R, Mongin D, Guemara R, et al. Incidence of major adverse cardiovascular events in patients with rheumatoid arthritis treated with Janus kinase inhibitors compared to biologic disease-modifying antirheumatic drugs: data from an international collaboration of registries (the "JAK-pot" study). Arthritis Rheumatol. Published online April 15, 2025. doi:10.1002/art.43188
