Clin Rheumatol DOI 10.1007/s10067-014-2718-8

BRIEF REPORT

Adalimumab decreases aortic stiffness independently of its effect in disease activity in patients with rheumatoid arthritis Dimitrios Vassilopoulos & Athanasios Gravos & Charalambos Vlachopoulos & Anna Kandili & Nikolaos Ioakeimidis & Dimitrios Pectasides & Christodoulos Stefanadis

Received: 10 February 2014 / Revised: 20 May 2014 / Accepted: 5 June 2014 # Clinical Rheumatology 2014

Abstract Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to traditional cardiovascular risk factors and/or the chronic systemic inflammation. We investigated the effect of a TNF antagonist (adalimumab-ADA) on aortic stiffness in RA patients. We studied 18 RA patients with active disease despite therapy with disease modifying antirheumatic drugs (DMARDs), treated with ADA (alone or in combination with DMARDs) for 12 weeks. Disease activity markers as well as aortic stiffness indices (carotid-femoral pulse wave velocityPWV, augmentation index-AIx), were measured at baseline and at the end of treatment. Eighteen RA patients treated with methotrexate (MTX) were included as controls. Patients were categorized as responders (decrease of Disease Activity Score-DAS28>1.2) or nonresponders. There was a statistically significant decrease in PWV (from 8.18±2.03 to 7.01± 1.78 m/s, p=0.00006) and DAS28 (from 6.65±1.22 to 4.69± 1.46, p=0.00007) in RA patients treated with ADA. The decrease in PWV was observed both in responders (n=12) and nonresponders (n=6). Multivariate analysis showed that the decrease of PWV was independent of changes in disease activity or other parameters. There was no significant change in PWV in patients treated with MTX (from 8.87±1.91 to 8.41±2.17, p=0.29). No significant change in AIx or traditional cardiovascular risk factors was observed. Treatment with ADA significantly reduced aortic stiffness in RA patients regardless of their response to therapy. These findings imply a D. Vassilopoulos (*) : A. Kandili : D. Pectasides 2nd Department of Medicine and Laboratory, Hippokration General Hospital, National University of Athens Medical School, 114 Vass. Sophias Ave., 115 27 Athens, Greece e-mail: [email protected] A. Gravos : C. Vlachopoulos : N. Ioakeimidis : C. Stefanadis 1st Department of Cardiology, Hippokration General Hospital, National University of Athens Medical School, Athens, Greece

direct protective effect of ADA in vascular wall in RA patients. Keywords Arterial stiffness . Methotrexate . Rheumatoid arthritis . TNF antagonists

Introduction Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, associated with increased cardiovascular mortality [12]. Even after adjustment for traditional cardiovascular risk factors, there is a higher rate of cardiovascular events in RA patients and this has been attributed in part to chronic inflammation [12]. Inflammation plays a significant role in the pathogenesis of atherosclerosis, and so far, there have been certain shared features between atherosclerosis and RA [12]. Tumor necrosis factor-a (TNF-a) is a pleiotropic, proinflammatory cytokine that plays a pivotal role in inflammation, both in RA and atherogenesis [15]. Treatment with TNF antagonists (anti-TNFs) has revolutionarized the treatment of RA by reducing joint and systemic inflammation. A number of studies have shown that anti-TNFs decrease cardiovascular events in RA patients [9], but thus far, it is unclear if this effect is due to its antiinflammatory activity, change in cardiovascular risk factors [6] or through a direct effect in the arterial wall [12]. Arterial stiffness and enhanced wave reflections are markers of cardiovascular disease and independent predictors of cardiovascular risk [21]. Increased arterial stiffness has been reported in RA, [3,10,13,19] although its role in predicting cardiovascular risk in this population has not been studied so far [12]. A number of studies have examined the effect of anti-TNFs on arterial stiffness with conflicting results [7], with limited data on the effect of synthetic DMARDs.

Clin Rheumatol

The aim of our study was to investigate the effect of adalimumab (ADA) on arterial stiffness in RA patients, according to its effect on disease activity.

Methods Thirty six consecutive patients with RA (according to the 1987 American Rheumatism Association criteria) [2] were recruited from the Outpatient Rheumatology Clinic of a referral tertiary care center (2nd Department of Medicine, Athens University School of Medicine, Hippokration General Hospital, Athens, Greece). Patients with cancer, pregnancy, heart failure (NYHA III–IV), active infection, tuberculosis or age 1.2) or nonresponders (DAS28 reduction

Adalimumab decreases aortic stiffness independently of its effect in disease activity in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to traditional cardiovascular risk factors an...
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