Background: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-alpha in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA.
Methods and results: Eleven RA patients (mean age 46+/-5 years; disease duration 9+/-2 years) with high disease activity despite treatment with stable doses of methotrexate (<or=25 mg/wk) and prednisone (<or=10 mg/d) were investigated. Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasound were measured before and after 12 weeks of infliximab therapy. Flow-mediated vasodilation improved from 3.2+/-0.4% to 4.1+/-0.5% (P=0.018), whereas endothelium-independent vasodilation with nitroglycerin and baseline diameter remained unchanged (13.6+/-1.2% versus 12.8+/-1.4%, P=0.98, and 3.74+/-0.15 versus 3.66+/-0.11 mm, P=0.54, respectively). Disease activity score (DAS28) was significantly reduced, from 5.6+/-0.3 to 3.5+/-0.6 (P=0.002). Erythrocyte sedimentation rate and C-reactive protein were lowered from 34+/-7 to 19+/-5 mm/h (P=0.04) and from 38+/-11 to 15+/-10 mg/L (P=0.08), respectively.
Conclusions: This is the first study to show that anti-TNF-alpha treatment improves endothelial function in RA. The data suggest that in RA, endothelial dysfunction is part of the disease process and is mediated by TNF-alpha.