Sustained improvement of vascular endothelial function during anti-TNFalpha treatment in rheumatoid arthritis patients.
OBJECTIVE
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.
Sidiropoulos
P I
PI
Department of Rheumatology, Clinical Immunology and Allergy, University of Crete Medical School, Heraklion, Greece.
Siakka
P
P
Pagonidis
K
K
Raptopoulou
A
A
Kritikos
H
H
Tsetis
D
D
Boumpas
D T
DT
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D014463:Ultrasonography
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab