AB0562 POTENTIAL BIOMARKERS OF PERSONALIZED TREATMENT BASED ON CARDIOVASCULAR-RELATED COMORBIDITIES IN PSORIATIC ARTHRITIS
Authors: I. Arias de la Rosa, M. D. López Montilla, C. Román-Rodriguez, I. Gómez García, M. J. Pérez Galán, I. Añón Oñate, M. D. C. Abalos-Aguilera, C. Perez-Sanchez, D. Ruiz, A. M. Patiño-Trives, M. Luque-Tévar, M. L. Ladehesa Pineda, C. López-Medina, C. Lopez-Pedrera, A. Escudero Contreras, E. Collantes Estevez, N. Barbarroja Puerto
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriatic Arthritis (PsA) displays increased traditional cardiovascular (CV) risk factors, such as insulin resistance (IR), metabolic syndrome or obesity. Thus, it is an urgent need to treat and manage these cardiometabolic comorbidities associated. Some evidence points out that methotrexate could improve CV risk due to its anti-inflammatory properties, however the effect of PDE4 inhibitor treatment on CV risk have not been elucidated yet. Objectives: 1) To evaluate the effect of conventional therapy and PDE4 inhibitor in PsA patients with high prevalence of cardiometabolic comorbidities. 2) To identify a molecular patient profile susceptible of being benefit from each therapy regarding disease activity and CV risk. Methods: Thirty biological-naïve patients with PsA were treated with the PDE4 inhibitor (Apremilast), Methotrexate or combined therapy (Apremilast and Methotrexate) following the clinical routine practice for 6 months. A cohort of 30 age and sex-matched healthy donors (HDs) was included. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of patients and HDs. Different parameters related to the cardiometabolic risk were analyzed, including: atherogenic index, ratio apolipoprotein B (apo B)/apolipoprotein A (apo A), insulin resistance (IR), metabolic syndrome, obesity, arterial hypertension, and the SCORE. Clinical and analytical parameters were collected: lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, apo A and apo B), glucose and insulin, body surface area (BSA) affected by psoriasis, number of tender and swollen joints, DAPSA, C-reactive protein and erythrocyte sedimentation rate. A panel of 92 proteins involved in cardiovascular disease (cardiovascular panel II, Olink) and an adipocytokine profile was measured in plasma and PBMCs. Hard cluster analysis was carried out in order to identify two distinctive molecular phenotypes depending on the treatment response related to the reduction of CV risk. Results: Among the 92 CV-related proteins, the higher levels of two molecules, CD163 and FABP4 observed in PsA patients compared to HDs, were strongly associated with elevated rates of CV risk factors such as apolipoprotein B/A and atherogenic risks, metabolic syndrome, obesity, IR, arterial hypertension and smoking. Thus, we could identify two clinical profiles of patients according to the plasma levels of these molecules: cluster 1 defined by 20 patients with low levels of CD163 and FABP4 and low prevalence of CV comorbidities and cluster 2 defined by 10 patients with high levels of CD163 and FABP4 and high prevalence of CVD comorbidities. Regarding cluster 2, those patients that were treated with Apremilast or combined therapy had a significant reduction of CD163 and FABP4 associated with a drop in total cholesterol, apo B, IR state and body mass index. In addition, both PDE4 inhibitor and combined treatment reduced activity disease. However, Methotrexate in monotherapy did not show a beneficial effect in PsA patients displaying higher levels of CD163, FABP4, total cholesterol and no changes in disease activity after treatment. In regard to cluster 1, the three therapy strategies reduced disease activity after 6 months. Even with low rates of comorbidities, those patients treated with Apremilast had reduced levels of total cholesterol and apolipoprotein B and body mass index after 6 months of therapy. However, no changes were observed in the treatment with Methotrexate or Methotrexate combined with Apremilast. Conclusion: 1- CD163 and FABP4 could be considered as potential biomarkers of treatment efficacy regarding cardiometabolic comorbidities. 2- Apremilast might target metabolic alterations in PsA modulating lipid profile, insulin resistance and body mass index, decreasing the levels of surrogate CV-related molecules. 3- Apremilast treatment should be considered in PsA patients with higher rates of cardiometabolic comorbidities. Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER. Disclosure of Interests: None declared.