EULAR 2023: How does tofacitinib affect cardiovascular risk in rheumatoid arthritis?

Importance of CV risk in RA

Cardiovascular diseases (CVD) including ischemic heart disease (IHD) and stroke are the main cause of premature mortality and sudden death in patients with RA. In addition to common CV risk, CV risk factors specific to the disease are also increased in RA. A key promoter of CVD is endothelial dysfunction (ED), and its modification is a major goal in efforts to reduce CV risk in rheumatoid arthritis. Therapeutic options are relatively limited, so the authors of the study prospectively examined the impact of tofacitinib use on CV risk in patients with active RA.

Methodology, course, and goals of the study

The randomized study included 81 patients with RA who met the 2010 Rheumatoid Arthritis Classification Criteria. All were undergoing stable antirheumatic therapy and for 12 weeks, half of the participants took tofacitinib at a dose of 5 mg twice a day (n = 41) and the other half took placebo (n = 40).

The median age of the study population was 54 years, with 81% being women. These were patients with moderate to high disease activity who did not respond to methotrexate at a dose of at least 15 mg per week and/or another synthetic disease-modifying antirheumatic drug (csDMARD) and had been treated for RA for a long time (average disease duration was approximately 14 years). At the same time, they did not have clinically apparent cardiovascular disease. Both groups did not differ significantly in mean BMI values (approximately 26 kg/m²) or blood pressure (normal in both arms). Positive rheumatoid factor (RF) was present in about half of the patients.

The primary endpoints included endothelial dysfunction assessed by flow-mediated dilation (FMD) test, both at the beginning and after 12 weeks of treatment, and the occurrence of major cardiovascular events (MACE) and venous thromboembolism (VTE) during the study. Secondary endpoints included disease activity score in 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and disability index values according to the Health Assessment Questionnaire (HAQ-DI).

Results

At the beginning, both groups had impaired endothelial function and elevated inflammatory markers and HAQ-DI values.

After treatment, it was found that in the tofacitinib-treated group, the FMD values significantly improved (from 6.64 ± 2.13% to 8.17 ± 2.69%; p = 0.0001), while no improvement was seen in the placebo group (change from 6.36 ± 3.01% to 6.84 ± 2.95%; p = 0.68). Post-tofacitinib treatment also showed improvements in DAS28, ESR, and CRP parameters (p ≤ 0.05 compared to placebo).

After 12 weeks of treatment, FMD in the tofacitinib group increased by 23.04%, while DAS28, ESR, and CRP values decreased by 31.23%, 29%, and 60%, respectively. A significant negative correlation was recorded between FMD and CRP (0.32; p < 0.05) before and after tofacitinib treatment (r = −0.34; p ≤ 0.05), while not in the placebo group.

The administration of tofacitinib compared to placebo also significantly reduced HAQ-DI values.

During the study, there were no occurrences of MACE or VTE in any group.

Conclusion

In this study, tofacitinib demonstrated not only its anti-inflammatory activity in patients with active RA without apparent CV disease but also its effect on mitigating endothelial dysfunction. This Janus kinase inhibitor may have a vasoprotective effect mediated by anti-inflammatory and possibly other mechanisms.

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Source: Syngle A., Verma I., Garg N. et al. POS0837 Impact of JAKi, tofacitinib, on CV risk in rheumatoid arthritis: JAKi CV risk impact study. Ann Rheum Dis 2023; 82: 716–717, doi: 10.1136/annrheumdis-2023-eular.6002.