SAT0331 Inflammatory markers and adipokines related to cardiovascular risk and metabolic comorbidities in psoriatic arthritis. in vivo effects of apremilast

2018 
Objectives 1) To evaluate the role of inflammatory mediators and adipokines in the cardiovascular risk profile and the metabolic comorbidities associated with psoriatic arthritis (PsA). 2) To evaluate the effect of apremilast in the adipocytokine pattern, metabolic components and endothelial dysfunction in patients with PsA and metabolic syndrome (MetSyn). Methods 55 PsA patients and 30 age and gender-matched healthy donors (HD) were analysed. An extensive clinical analysis including body index mass, lipid profile, HOMA-IR and intra-arterial blood pressure was performed. Endothelial function was measured through post occlusive hyperemia using Laser-Doppler. Different proinflammatory cytokines (TNFa, IL1b and IL6), vascular adhesion molecules (VEGF and E-Selectin) and adipokines (adiponectin, leptin, resistin and visfatin) were analysed on serum by ELISA. Ten biological-naive patients with PsA having metabolic syndrome were given apremilast 30 mg twice daily for 6 months. All the measures were carried out at basal, week 4 and week 24 after apremilast treatment. Results The prevalence of metabolic comorbidities such as MetSyn, obesity and insulin resistance (IR) was significant higher in PsA compared to HD. PsA patients had impaired endothelial function showed by a reduced peak flow and hyperaemia area and increased levels of VEGF and E-Selectin in serum. The levels of adipocytokines were significantly higher in PsA compared to HD. The body mass index values were significantly correlated with the clinical inflammatory parameters (CRP and ESR) and activity of the disease (swollen joints count and DAS28). Increased levels of HOMA-IR also correlated with DAS28, clinical and serological inflammatory markers, and diverse adipokines. Elevated levels of cytokines correlated with the activity of the disease and lipid alterations. Significant improvements in efficacy outcomes, including DAS-28 using erythrocyte sedimentation rate (ESR), tender and swollen joint count, Visual Analogue Scale (VAS), enthesitis and morning stiffness severity, were observed with apremilast at week 4. No changes on BMI were noticed. A significant reduction of intra-arterial blood pressure was evidenced since the first 4 weeks. Serum levels of Apolipoprotein A and B, insulin and HOMA-IR values were also significantly reduced after 24 weeks of treatment. Endothelial dysfunction was significantly restored shown by an increase of the peak flow and hyperaemia area and decreased adhesion molecules in serum. Levels of interleukins and adipokines were also modulated after apremilast treatment. Conclusions PsA is associated with an increase in inflammatory cytokines and adipokines, alongside with an endothelial dysfunction. These alterations are related to the disease activity and the presence of metabolic comorbidities such as insulin resistance or obesity, contributing to the burden of cardiovascular disease risk. Apremilast might reduce IR, inflammation, hypertension, lipids and endothelial dysfunction, parameters strongly involved in cardiovascular disease. Acknowledgements Supported by the Minister of Health (ISCIII, PI17/01316, RIER RD16/0012/0015) cofinanced with FEDER funds. Disclosure of Interest None declared
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