Insights from EULAR 2025: JAK Inhibitors' Cancer and Cardiovascular Safety

At the 2025 annual congress of the European Alliance of Associations for Rheumatology (EULAR) held in Barcelona, recent findings emerged regarding the safety profiles of Janus kinase (JAK) inhibitors in relation to cancer and cardiovascular risks, particularly among rheumatoid arthritis (RA) patients. This research adds significant insights to an ongoing debate about the therapeutic use of JAK inhibitors, especially concerning their long-term implications.

The study, led by Dr. Romain Aymon from the University of Geneva, analyzed data from 13 international registers, involving over 33,000 patients. It aimed to compare cancer incidence among RA patients treated with JAK inhibitors versus those receiving biologic disease-modifying anti-rheumatic drugs (bDMARDs). The findings revealed that, overall, patients treated with JAK inhibitors did not exhibit a significantly higher risk of cancer compared to those on bDMARDs. Specifically, the crude incidence of non-melanoma skin cancers (NMSC) was reported at 2.2 per 1,000 patient-years for tumor necrosis factor inhibitors (TNFi), 2.9 for JAK inhibitors, and 3.1 for bDMARDs with other mechanisms of action (OMA). Notably, statistical analysis did not indicate a significant difference in cancer incidence between the treatment groups (Aymon et al., 2025).

Despite these findings, the study highlighted that patients aged 50 and older with at least one cardiovascular risk factor exhibited a higher cancer incidence across all treatment groups. This cohort demonstrated rates of 3.2, 4.2, and 4.1 per 1,000 patient-years for TNFi, JAK inhibitors, and OMA, respectively. However, again, no significant differences were found between JAK inhibitors and other treatments in terms of cancer risks (Aymon et al., 2025).

Additionally, the research presented by Dr. Viking Huss from the Swedish Rheumatology Quality Register pointed to a concerning trend regarding keratinocyte cancers. The analysis found that treatment with JAK inhibitors was associated with a higher incidence of first keratinocyte cancers, particularly basal cell carcinomas. The hazard ratio for developing keratinocyte cancer was 1.72 for JAK inhibitors compared to TNFi (Huss et al., 2025). This indicates a need for increased dermatological monitoring for patients on JAK inhibitors to manage skin cancer risks effectively.

In a complementary study, Dr. Asmaa Beltagy from the University of Cairo presented findings on glucagon-like peptide-1 receptor agonists (GLP-1RA) and their potential cardioprotective effects for RA patients on JAK inhibitors. The retrospective analysis of 2,449 RA patients showed that those taking GLP-1RA displayed a significantly lower risk of acute coronary syndromes and deep venous thrombosis compared to those who did not. The overall incidence of cardiovascular events was notably lower in the GLP-1RA group, although some outcomes did not achieve statistical significance (Beltagy et al., 2025).

The implications of these findings are substantial for rheumatologists and patients alike. The reassurance regarding cancer risks associated with JAK inhibitors may encourage their continued use in treating RA. However, the heightened risk of keratinocyte cancers necessitates vigilant monitoring of skin health among these patients. Furthermore, the potential cardiovascular benefits of GLP-1RA offer an exciting avenue for enhancing treatment regimens for RA patients, particularly those at elevated cardiovascular risk.

While the data presented at EULAR 2025 is promising, researchers underscore the importance of further studies to validate these findings and explore the long-term implications of JAK inhibitors and GLP-1RA on cancer and cardiovascular health. Continuous monitoring and research are essential to ensure optimal patient care in the evolving landscape of rheumatology treatments.