Elderly patients with rheumatoid arthritis may experience measurable improvements in cerebral blood flow and vascular function when treated with the TNF-α inhibitor etanercept, according to findings from a randomised controlled trial. The study provides new evidence linking systemic inflammation control to cerebrovascular health in older patients with rheumatoid arthritis.
Study Design and Clinical Assessments
The single-center, prospective randomized trial enrolled 159 elderly patients with mild rheumatoid arthritis disease activity. Participants were randomly assigned to receive either combination therapy with etanercept, methotrexate, and celecoxib, or standard therapy with methotrexate and celecoxib alone. Cerebral hemodynamics were assessed at baseline and after six months of treatment using transcranial Doppler ultrasonography.
Key cerebrovascular parameters included mean flow velocity of the middle cerebral artery, pulsatility index, resistance index, and cerebrovascular reactivity measured by the breath-holding index. In parallel, investigators evaluated inflammatory markers and endothelial function indicators, including C-reactive protein, erythrocyte sedimentation rate, TNF-α, interleukin-6, soluble vascular cell adhesion molecule-1, and endothelin-1.
Improvements in Cerebral Blood Flow and Vascular Reactivity
After six months, patients receiving etanercept demonstrated significantly higher middle cerebral artery flow velocities alongside reductions in pulsatility and resistance indices compared with the control group. Cerebrovascular reactivity also improved substantially, indicating enhanced cerebral blood flow regulation.
These hemodynamic improvements were accompanied by broad reductions in systemic inflammatory markers and endothelial dysfunction indicators. Correlation analyses showed that improvements in cerebrovascular reactivity were significantly associated with reductions in TNF-α, soluble vascular cell adhesion molecule-1, and endothelin-1, suggesting a mechanistic link between inflammation suppression and vascular function.
Safety and Clinical Implications
Adverse event rates were similar between treatment groups, with no statistically significant differences observed. The authors conclude that etanercept may improve cerebral hemodynamics and cerebrovascular reserve in elderly patients with rheumatoid arthritis, potentially reducing the elevated risk of cerebrovascular events seen in this population.
These findings support the concept that targeted anti-TNF therapy may offer benefits beyond joint disease control, with implications for cardiovascular and cerebrovascular risk management in older patients with inflammatory arthritis.
Reference
Ren Q et al. TNF-α inhibitor etanercept improves cerebrovascular function in elderly RA patients: findings from a randomized controlled trial. BMC Rheumatol. 2025;DOI: doi.org/10.1186/s41927-025-00589-6.
