Background: Endothelial function and arterial stiffness are significantly worse in rheumatoid arthritis (RA) compared to healthy controls in part due to the high-grade inflammation. In non-RA subjects, elevated serum levels of interleukin (IL)-6 are associated with accelerated atherosclerosis. Objectives: To examine whether therapeutic blockade of IL-6 receptor by tocilizumab in patients with active RA improves endothelial dysfunction and increases arterial elasticity.

Methods: In 11 non-diabetic women with RA (aged 44.5±9.9 years, mean±SD) without concomitant cardiovascular disease, who had documented endothelial dysfunction (defined by flow mediated dilatation (FMD) of the brachial artery: <5%), we assessed (i) endothelial function by FMD and (ii) central arterial stiffness (by carotid-femoral pulse wave velocity (PWV)) at baseline after 3 and 6 months of treatment with tocilizumab (8mg/kg IV/28 days).

Results: FMD improved significantly after 3 months and this improvement was sustained at 6 months [FMD (%) from 3.3±0.8 to 6.4±1.3 and 5.2±1.9, respectively, p=0.003 for trend by Friedman test]. PWV showed significant progressive amelioration after each trimester of TCZ treatment [PWV (m/sec) from 8.2±1.2 to 7.7±1.3 and 7.0±1.0, respectively: p<0.001 for trend by Friedman test] without alteration of the mean arterial blood pressure. High sensitivity reactive protein (hs-CRP) decreased dramatically from 20.4±23.2 to 5.9±5.9 and 3.9±3.20 mg/dl, whereas the atheromatic index, defined as total cholesterol/high density cholesterol, remained unchanged (from 3.4±1.1 to 3.1±0.8 and 3.0±0.6).

Conclusions: Short-term treatment with tocilizumab reversed endothelial dysfunction and improved arterial elasticity in a pilot study of RA patients, possibly via decreases of the systemic inflammatory burden.