Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with increased cardiovascular risk (CVR). Treating disease activity with biologic and synthetic disease-modifying antirheumatic drugs (DMARDs) may reduce CVR. Disease activity is an important factor that negatively impacts CVR, but its effects on patients receiving biologic and targeted synthetic DMARDs are poorly understood. Echo-tracking parameters of the carotid artery can reveal arterial stiffness, a surrogate marker of subclinical atherosclerosis.

Objectives: To determine how disease activity affects markers of arterial stiffness in patients treated with biologic and targeted synthetic DMARDs.

Methods: A cross-sectional analysis was conducted on RA patients (disease duration ≥6 months) treated with TNF inhibitors (TNFi) or the JAK inhibitor upadacitinib (UPA), along with healthy controls who underwent ultrasound examination of the carotid artery using the Aloka ProSound Alpha 7. Patients with known atherosclerotic heart disease, diabetes, history of heart failure, stroke, arrhythmias, or chronic kidney disease were excluded. The measurements included pulse-wave velocity (PWVβ), beta-stiffness, augmentation index (AI), arterial compliance (AC), and elastic modulus (Ep), along with laboratory lipid parameters. Disease activity was assessed using Disease Activity Score 28 (DAS28-CRP, DAS28-ESR) and the Clinical Disease Activity Index (CDAI). Data were analyzed using SPSS v29. Statistical differences between the JAK and TNFi treatment groups were assessed using the Kruskal-Wallis test. A multivariate linear regression analysis was conducted to determine how markers of arterial stiffness were affected by composite tools measuring disease activity.

Results: A total of 109 subjects were included: 37.6% (n=41) treated with TNFi (adalimumab n=27, etanercept n=8, certolizumab pegol n=6), 34.9% (n=38) treated with JAK inhibitor upadacitinib, and 27% (n=30) healthy controls. The median age was 55 years (SD 11.5; range 20–78), and the median disease duration was 10 years (SD 7.24; range 2–30), with no differences between groups. The median treatment duration was 3 years (SD 3.65; range 0.5–18), with longer treatment duration in the TNFi group compared to the JAK group (4 vs. 2 years, p<0.001). No significant differences in arterial stiffness markers were found between the TNFi and JAK groups. However, in the JAK group, PWV, beta-stiffness, and Ep were higher compared to the control group (PWV 6.45 vs. 5.80, p=0.017; beta-stiffness 8.25 vs. 6.55, p=0.031; Ep 110 vs. 86.5, p=0.02). Multivariate regression analysis revealed that age (β=0.0537; 95% CI 0.0156–0.0918, p=0.006) and CDAI (β=0.1393; 95% CI 0.0337–0.2448, p=0.01) were significant predictors of PWV increase. Age and CDAI also predicted beta-stiffness (age: β=0.1741; 95% CI 0.04532–0.303, p=0.009; CDAI: β=0.4817; 95% CI 0.11136–0.862, p=0.012). No significant correlations were observed for DAS28-ESR or DAS28-CRP.

Conclusion: While aging plays a role in arterial stiffening in RA patients, disease activity, as measured by CDAI, is a significant driver of vascular damage. This relationship was not observed with DAS28-ESR or DAS28-CRP. These findings may reflect distinct anti-inflammatory effects of TNF and JAK inhibitors.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.