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)

Objective: To assess the incidence of major adverse cardiovascular events (MACE) in RA patients treated with JAKi, TNF-inhibitors (TNFi) or biologic Disease-Modifying Anti-Rheumatic Drugs with other modes of action (bDMARD-OMA) in a multi-country, real-world population.

Methods: RA patients from 15 registries in the JAK-pot collaboration were included. MACE incidence was analysed using two approaches: a within-registry analysis aggregating country-specific estimates from registers with >25 incident MACE events through meta-analysis, and an individual-level data combined analysis. We used adjusted linear mixed Poisson regression to obtain incidence rate ratios (IRR) of MACE between treatment groups, accounting for multiple treatment courses.

Results: The study included 73’008 treatment courses (16’417 JAKi, 35’373 TNFi and 21’218 bDMARD-OMA) and 828 incident MACE among 51’233 patients. Median follow-up time was 1.3 years, with most of the follow-up concentrated in the first two years of treatment. Incidence rates were 7.0, 7.6 and 11.8 per 1’000 person-years for JAKi, TNFi and bDMARD-OMA, respectively. Compared to TNFi, JAKi (within-registry adjusted IRR: 0.89, 95%CI 0.63 to 1.25)) had similar incidence rates of MACE and bDMARD-OMA had higher rates (within-registry adjusted IRR: 1.35, 95%CI 1.10 to 1.66). Combined analysis showed similar results.

Conclusion: 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.