Large International Study Finds No Increased Heart Risk from JAK Inhibitors in Rheumatoid Arthritis Patients

A comprehensive international study conducted by researchers at Geneva University Hospital has provided reassuring news regarding the safety of Janus kinase inhibitors (JAKi) in the treatment of rheumatoid arthritis (RA). The study, published in Arthritis & Rheumatology, analyzed data from over 51,000 patients across 15 national registries, totaling more than 73,000 treatment courses. Most of these courses occurred within the first two years of therapy.

Rheumatoid arthritis is a chronic autoimmune disease characterized by joint inflammation, structural damage, and persistent pain. Beyond joint issues, RA patients face a higher risk of cardiovascular events, which contribute to increased mortality. While traditional risk factors partially explain this elevated risk, systemic inflammation and lipid profile changes are also believed to play significant roles.

Although JAK inhibitors have offered a novel therapeutic option, they have been scrutinized for potential safety concerns. Previous clinical trials indicated a trend toward higher rates of major cardiovascular events with drugs like tofacitinib, though these findings were not statistically definitive. Regulatory agencies in Europe and the US issued warnings pending further clarification.

The recent study, known as the 'JAK-pot' study, aimed to clarify these safety concerns by comparing cardiovascular event rates among RA patients treated with JAKi versus those on tumor necrosis factor inhibitors (TNFi) or other biologic therapies. The researchers used advanced statistical modeling to account for various patient differences and treatment factors.

Findings revealed 828 major cardiovascular events during the observation periods. The incidence rates per 1,000 person-years were comparable across treatment groups, with 7.0 for JAKi, 7.6 for TNFi, and 11.8 for other biologic therapies. The analysis showed no significant increase in cardiovascular risk associated with JAKi, with adjusted incidence rate ratios close to or below 1 when compared to TNFi.

These results were consistent across multiple analyses, including different registry data and patient subgroups, even among those with higher baseline cardiovascular risk. The findings offer strong evidence that JAK inhibitors do not elevate the risk of major adverse cardiovascular events compared to established RA therapies.

This extensive research provides reassurance for clinicians and patients considering JAK inhibitors as part of their RA treatment plans, emphasizing that these therapies do not appear to carry additional heart risks in the short to medium term. Continued long-term monitoring and research are essential to further confirm these findings.

For more detailed information, see the original study: Romain Aymon et al, Incidence of major adverse cardiovascular events in patients with rheumatoid arthritis treated with Janus kinase inhibitors, published in Arthritis & Rheumatology, 2025.