Sustained improvement of vascular endothelial function during anti-TNFalpha treatment in rheumatoid arthritis patients

Scand J Rheumatol. 2009 Jan-Feb;38(1):6-10. doi: 10.1080/03009740802363768.

Abstract

Objectives: Vascular endothelial function and common carotid artery intima-medial thickness (CCA-IMT) are well-established surrogate markers for early atherosclerotic disease, which accounts for 30-40% of excess mortality in rheumatoid arthritis (RA) patients. Our aim was to investigate whether long-term treatment with anti-tumour necrosis factor (TNF)alpha agents can modulate endothelial function and CCA-IMT.

Methods: Twelve patients with RA (mean age 54.8+/-15 years) on anti-TNFalpha treatment (seven adalimumab, five infliximab) due to uncontrolled disease activity, with mean Disease Activity Score (DAS28) 5.7 (range 4.6-6.9) despite disease-modifying anti-rheumatic drugs (DMARDs), were studied prospectively. Patients were assessed at baseline and after 3 and 18 months for endothelial-dependent vasodilatation, assessed by flow-mediated vasodilatation (FMD), endothelial-independent vasodilatation and CCA-IMT. RA disease activity and response to therapy were assessed by the DAS28 index.

Results: After 18 months of treatment, 67% of the patients were responders according to European League Against Rheumatism (EULAR) response criteria. Anti-TNFalpha treatment improved FMD (from 7+/-4.3% to 11.1+/-3.8%, p = 0.026) whereas CCA-IMT did not change significantly [from 0.67 (0.4-1) to 0.68 (0.39-1.2) mm; mean change 0.01 (-0.06 to 0.08) mm]. Endothelial-independent vasodilatation remained stable (20.4+/-7.3% to 22.9+/-6.5%, p = 0.4).

Conclusions: In this small cohort of patients with RA and no clinically overt cardiovascular disease (CVD), after 18 months of treatment with anti-TNFalpha agents, endothelial function improved significantly while CCA-IMT remained stable. Longitudinal studies using more patients are needed to determine the clinical significance of these findings in relation to the risk of atherosclerosis.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / drug effects
  • Brachial Artery / pathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / drug effects
  • Tunica Intima / pathology
  • Tunica Media / diagnostic imaging
  • Tunica Media / drug effects
  • Tunica Media / pathology
  • Ultrasonography

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab