JAK Inhibitors Not Associated with Increased Cardiovascular Risk in RA Patients: Study

A new study published in the journal of Arthritis & Rheumatology showed that Janus kinase (JAK) inhibitors did not increase the risk of major cardiovascular events when compared to TNF inhibitors or other DMARDs. This large-scale analysis provides reassurance regarding the cardiovascular safety of JAK inhibitors in RA management.

When left untreated, rheumatoid arthritis (RA), an inflammatory disease, can cause chronic joint inflammation, gradual structural joint deterioration, and ongoing discomfort. Due to a higher risk of cardiovascular events in RA patients than in the general population, the condition is linked to a higher mortality rate. The most recent RA medications created are JAK inhibitors (JAKi). They are now a key component of the treatment arsenal against RA and have demonstrated significant promise in its management. 

According to current treatment guidelines, JAKi should only be administered once relevant cardiovascular disease risk factors have been taken into account. Therefore, Romain Aymon and team evaluated the incidence of major adverse cardiovascular events (MACEs) in a multi-country, real-world population of patients with RA receiving treatment with biologic disease-modifying antirheumatic drugs with other modes of action (bDMARD-OMA), tumor necrosis factor inhibitors (TNFi), or JAK inhibitors.

RA patients from 15 registries in the JAK-pot consortium were included. An individual-level data combination analysis and a within-registry analysis that aggregated country-specific estimates from registers with >25 incident MACEs by meta-analysis were used to investigate MACE incidence. To calculate the incidence rate ratios (IRRs) of MACEs between treatment groups while taking into consideration several treatment courses, this research employed modified linear mixed Poisson regression.

The study comprised 828 incident MACEs among 51,233 patients and 73,008 therapy sessions (16,417 JAKi, 35,373 TNFi, and 21,218 bDMARD-OMA). The majority of the follow-up took place within the first 2 years of therapy, with a median follow-up duration of 1.3 years. JAKi, TNFi, and bDMARD-OMA had respective incidence rates of 7.0, 7.6, and 11.8 per 1,000 person-years.

The incidence rates of MACEs were comparable for JAKi (within-registry adjusted IRR 0.89, 95% CI 0.63–1.25) and higher for bDMARD-OMA (within-registry adjusted IRR 1.35, 95% CI 1.10–1.66) than for TNFi. The outcomes of the combined analysis were comparable.

Overall, based on these findings, individuals with RA receiving JAKi treatment do not, on average, have a higher risk of MACEs than those receiving alternative bDMARDs, especially during the first 2 years of treatment.

Source:

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. (2025b). Incidence of major adverse cardiovascular events in patients with rheumatoid arthritis treated with JAK inhibitors compared with biologic disease-modifying antirheumatic drugs: Data from an international collaboration of registries. Arthritis & Rheumatology. https://doi.org/10.1002/art.43188