Article Impact Level: HIGH Data Quality: STRONG Summary of Arthritis & Rheumatology, art.43188. https://doi.org/10.1002/art.43188 Romain Aymon et al.
Points
- This extensive multinational study assessed cardiovascular event rates among rheumatoid arthritis patients using JAK inhibitors, TNF inhibitors, and other biologic therapies across over 73,000 treatment courses.
- JAK inhibitors and TNF inhibitors showed similar rates of major adverse cardiovascular events, while biologics with other mechanisms had a modestly higher risk.
- Specifically, MACE rates were 7.0 per 1,000 person-years for JAKi, 7.6 for TNFi, and 11.8 for bDMARD-OMA, indicating comparable cardiovascular safety between JAKi and TNFi.
- No increased cardiovascular risk was observed for JAK inhibitors, even in patients with elevated baseline cardiovascular risk, reinforcing their safety in real-world clinical use.
- These findings support the short-term cardiovascular safety of JAK inhibitors in RA treatment while calling for continued surveillance of long-term outcomes, especially for non-TNFi biologics.
Summary
In this international, multi-center observational study, the incidence of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), and biologic disease-modifying anti-rheumatic drugs with other mechanisms of action (bDMARD-OMA) was assessed. The study included 73,008 treatment courses from 51,233 patients across 15 registries. The median follow-up time was 1.3 years, with most follow-up concentrated in the first two years. The study found MACE rates of 7.0 per 1,000 person-years for JAKi, 7.6 per 1,000 person-years for TNFi, and 11.8 per 1,000 person-years for bDMARD-OMA.
When comparing JAKi to TNFi, no significant difference in MACE incidence was observed, with an incidence rate ratio (IRR) of 0.89 (95% CI: 0.63–1.25). In contrast, bDMARD-OMA was associated with a higher incidence rate, with an IRR of 1.35 (95% CI: 1.10–1.66). The combined analysis across 14 registries corroborated these findings, confirming that JAKi did not increase the incidence of MACE compared to TNFi. The study’s results were consistent across subgroups, including those with elevated cardiovascular risk, and no evidence suggested a higher cardiovascular risk with JAKi compared to TNFi.
The findings of this study offer reassurance regarding the cardiovascular safety of JAKi treatment in RA patients during the initial two years of therapy, showing no increased risk compared to TNFi. While biologic therapies with other mechanisms of action demonstrated a modestly higher risk, the findings highlight the need for continued monitoring and further research on the long-term cardiovascular effects of these treatments. This research contributes to the growing body of evidence on the safety of JAKi in the real-world clinical setting.
Link to the article: https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.43188
References Aymon, R., Mongin, D., Guemara, R., Salis, Z., Askling, J., Choquette, D., Codreanu, C., Di Giuseppe, D., Flouri, I., Huschek, D., Hyrich, K. L., Iannone, F., Kvien, T. K., Leeb, B. F., Nordström, D., Otero‐Varela, L., Pavelka, K., Pombo‐Suarez, M., Rodrigues, A., … Lauper, K. (2025). 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 & Rheumatology, art.43188. https://doi.org/10.1002/art.43188
