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TNF-alpha blockade induces a reversible but transient effect on endothelial dysfunction in patients with long-standing severe rheumatoid arthritis

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Abstract

Considerable evidence indicates that patients with rheumatoid arthritis (RA) are at greater risk of developing atherosclerosis and cardiovascular disease. Recent studies support the predictive ability of endothelial function measures for subsequent atherosclerotic events. We have investigated the effects of infliximab, a chimeric monoclonal anti-tumor necrosis factor (TNF) antibody, on endothelial vasodilation, measured by brachial ultrasonography and on the levels of inflammatory biomarkers and adhesion molecules in ten consecutive patients with severe long-standing RA, despite methotrexate therapy, during the loading phase of infliximab therapy. Flow-mediated dilation (FMD) in RA patients at baseline was significantly impaired compared with healthy controls (7.71 ± 2.78% vs 14.91 ± 6.41%; p = 0.008) and improved significantly after infliximab infusion (12.63 ± 1.63% vs 7.71 ± 2.78%; p = 0.005). At baseline, a statistically significant correlation between C-reactive protein levels and FMD was found (r = −0.69, p = 0.026). However, this improvement was transitory, as FMD values returned to baseline values before each infliximab infusion at weeks 2, 6 and 14. There were no significant differences in baseline brachial artery diameter between visits, although at each time, the diameter was increased. According to European League Against Rheumatism response criteria, all ten patients were good responders. No significant differences were observed in intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, vascular endothelial growth factor and E-selectin plasma levels before and after each infusions. This study demonstrates that endothelial dysfunction is a reversible phenomenon in RA. The addition of anti-TNFα treatment reduces inflammatory symptoms in patients with severe RA. The improvement of endothelial function during the loading phase of therapy is transitory, suggesting an enhanced and persistent TNF-α generation within the arterial wall.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Catholic University of the Sacred Heart, via G. Moscati, 31-00168, Rome, Italy

    Silvia Bosello, Angelo Zoli & GianFranco Ferraccioli

  2. Division of Angiology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy

    Angelo Santoliquido, Cristiana Di Campli, Roberto Flore & Paolo Tondi

Authors
  1. Silvia Bosello
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  2. Angelo Santoliquido
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  3. Angelo Zoli
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  4. Cristiana Di Campli
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  5. Roberto Flore
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  6. Paolo Tondi
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  7. GianFranco Ferraccioli
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Correspondence to GianFranco Ferraccioli.

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Bosello, S., Santoliquido, A., Zoli, A. et al. TNF-alpha blockade induces a reversible but transient effect on endothelial dysfunction in patients with long-standing severe rheumatoid arthritis. Clin Rheumatol 27, 833–839 (2008). https://doi.org/10.1007/s10067-007-0803-y

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  • DOI: https://doi.org/10.1007/s10067-007-0803-y

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