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

Abstract

Objectives1) 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).Methods55 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-naïve 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.ResultsThe 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.ConclusionsPsA 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.Ackno...

Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers

“…There is significant evidence demonstrating that type 2 diabetes mellitus, obesity, metabolic syndrome and cardiovascular disease are characterized by a low grade of intestinal inflammation, due to gut dysbiosis. Moreover, PsA is associated with an increased level of pro‐inflammatory cytokines and adipokines in patients with metabolic comorbidities 21,22 . Indeed, 27 of our enrolled outpatients were affected by major cardiovascular disorders, as already reported in our data.…”

“…In this scenario, apremilast reduces the parameters strongly associated with cardiovascular disease, such as insulin resistance, inflammation, hypertension and lipid metabolism. Apremilast also contributes to restore endothelial disfunction, limiting cardiovascular disease risk 21,22 . Moreover, the molecule demonstrated to be an excellent metabolic regulator acting also on atherosclerotic plaque stabilization, blocking its progression 23 .…”

Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?

“…Inhibition of PDE4 improves liver steatosis, reduces lipid deposition in the liver and consequently improves insulin resistance (89). Apremilast also appears to contribute to counteracting endothelial dysfunction, thus reducing CV risk (91,92), and to stabilize atherosclerotic plaques, hence blocking its evolution to an unstable, high risk phenotype (93). An interesting study conducted by Mazzilli and coworkers observed a better therapeutic response to apremilast in diabetic patients compared to non-diabetic patients, with a reduction in blood glucose and total-and LDLc levels (94).…”

The Use of Apremilast in Psoriasis: An Indian Perspective on Real-World Scenarios

“… 43 Similarly, De La Rosa et al concluded that apremilast may reduce insulin resistance, inflammation, hypertension, lipids, and endothelial dysfunction. 44 Liu et al reported that apremilast reduces the formation of atherosclerotic plaque; thus, it may be useful for the treatment and prevention of atherosclerosis. 45…”