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Background:The presence of cardiovascular disease in psoriatic arthritis (PsA) is of particular concern, as it is considered the leading cause of mortality in PsA. Thus, it is essential to recognize those appropriate therapies that could target this comorbidity, reducing the risk of cardiovascular disease and metabolic alterations.Objectives:To evaluate the efficacy of methotrexate (MTX) and apremilast as monotherapies or in combination, in the clinical manifestations of the disease and the reduction of cardiovascular risk factors in PsA.Methods:Prospective longitudinal study in 30 PsA patients diagnosed according to CASPAR criteria: 10 patients were treated with MTX (12 ± 2,58 mg/week), 10 patients with apremilast (60 mg/day) and 10 were treated with combined therapy for 6 months, recruited in the routine clinical practice at the Reina Sofia Hospital of Cordoba and University Hospital of Jaen, Spain. Clinical and analytical parameters were collected at baseline and after 6 months of treatment: lipid profile (cholesterol, HDL, LDL, TG, ApoA and ApoB), glucose and insulin, body surface area (BSA) affected by psoriasis, number of tender and swollen joints, DAS28, DAPSA, VAS, CRP and ESR.The presence of cardiometabolic risk factors such as metabolic syndrome (MetSyn) was evaluated according to National Cholesterol Education Program (NCEP) adult treatment panel III (ATP III) criteria, meeting 3 of the following characteristics: abdominal obesity (men (>102 cm); women (>88 cm), TG > 150 mg/dL, HDL (men ( 130/85 mmHg, glucose levels > 110 mg/dL). Insulin resistance (HOMA-IR > 2,5), body mass index (BMI), ApoB/ApoA ratio, atherogenic index (AI) and SCORE (age, gender, cholesterol, HDL, smoking habit and diabetes) were also studied.Results:Apremilast or MTX monotherapies caused a moderate reduction of the clinical inflammatory markers (CRP and ESR) and disease activity (VAS, DAPSA and DAS28) after 6 months of treatment. On the other hand, while apremilast significantly reduced the affected BSA, MTX had no significant effect. All those parameters were more significantly reduced after the combined treatment (MTX+ apremilast).Apremilast monotherapy significantly improved alterations in the lipid profile (reducing cholesterol and LDL levels, ApoB/ApoA ratio and AI), insulin resistance and decreased BMI, thus reducing the number of patients with MetSyn. MTX monotherapy treatment had no positive effect on these parameters. None of the treatments had significant effects on SCORE values.The beneficial effects of apremilast on the lipid profile were mitigated after the combination with MTX. Nevertheless, the number of patients with MetSyn decreased even more after the combined therapy of MTX with apremilast compared to apremilast monotherapy.Conclusion:1) In patients with moderate disease activity, treatment with apremilast monotherapy might have some advantages compared to the MTX monotherapy, since it can decrease the percentage of BSA with psoriasis, the lipid profile alteration, IR and weight, thus improving the cardiovascular risk profile. 2) Combined therapy (MTX+ apremilast) can induce a deeper reduction in the disease activity compared to the monotherapies, maintaining, in turn, the positive effects of apremilast on the cardiovascular risk.Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER.Disclosure of Interests:Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene., Iván Arias de la Rosa: None declared, Carmen Torres-Granados: None declared, Maria del Carmen Abalos-Aguilera: None declared, Gómez García Ignacio: None declared, Isabel Añón Oñate: None declared, María José Pérez Galán: None declared, Desiree Ruiz: None declared, Alejandra M. Patiño-Trives: None declared, María Luque-Tévar: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene, Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Alejandro Escudero Contreras Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene., María Dolores López Montilla Speakers bureau: Celgene

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.

Background:Apremilast (APR) is a phosphodiesterase 4 Inhibitor. APR has been demonstrated to be an effective and safe therapy in the treatment of active psoriatic arthritis (PsA) and psoriasis in patients who were intolerant of or unresponsive to synthetic Disease-modifying Antirheumatic Drugs (DMARDs).Objectives:To assess the effectiveness and survival rates of APR in a cohort of patients diagnosed with PsA and psoriasis with arthritis in real clinical practice.Methods:An open, longitudinal, prospective, descriptive study. A total of 80 patients diagnosed with PsA or psoriasis with arthritis were included. All patients received the starting dose of oral APR as per the Summary of Product Characteristics and a maintenance dose of 30mg every 12 hours. The following variables were collected: age, gender, years of evolution, prior treatment with DMARDs, swollen and tender joint counts (SJC, TJC), C-Reactive Protein (CRP), and presence of dactylitis, enthesitis and cutaneous psoriasis. Treatment response was evaluated in all patients at 6, 12 and 18 months follow-ups. Efficacy in patients with PsA was evaluated using the Disease Activity in Psoriatic Arthritis (DAPSA)-based criteria: low activity (DAPSA 5-14) and clinical remission (DAPSA 0-4). To assess the level of enthesitis, Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) index was used. Efficacy in patients with psoriasis was evaluated using the Psoriasis Area and Severity Index (PASI)-based criteria: PASI-75 (improvement ≥ 75% of the baseline PASI). Kaplan-Meier method was used for survival analysis.Results:Of the 80 patients included in our cohort: 42 patients were diagnosed with PsA and 38 with psoriasis. 57,1% of patients with PsA and 63,2% of patients with psoriasis were men with a mean age of 48.2 ± 11.1 and 48.2 ± 14.8 and mean duration of disease 3.5 ± 1.4 and 3.2 ± 2.6 years respectively. Most of the patients with PsA (93%) had cutaneous disease and enthesitis and dactylitis were present in 45% and 31% respectively. 95% of patients with PsA had received prior treatment with Metotrexate. At 6, 12 and 18 months, there was a statistically significant decrease from baseline in TJC, SJC and DAPSA scores. The decrease in the MASES index and the levels of PCR were not statistically significant (Table 2). According to DAPSA, at 18 months follow-ups, clinical remission rate was 77.8%, and low activity rate was 22.2%. 55% of patients with psoriasis reached PASI-75 at 18 months. APR survival rates at 6, 12 and 18 months was 67,85 %, 56,45% and 50,2 % in patients with ApS and 74,8%, 70,4% and 65,1 % in patients wiyh psoriasis.Conclusion:APR is an effective drug for the treatment of psoriatic arthritis and psoriasis, reaching statistical significance according to DAPSA, and with a high survival rate after 18 months of treatment.References:[1]Goldenberg G, Lanoue J, Dong J. New oral therapies for psoriasis: a comprehensive review. J Clin Aesthet Dermatol. 2016;9(8):25–8.[2]Reed M, Crosbie D. Apremilast in the treatment of psoriatic arthritis: a perspective review. Ther Adv Musculoskelet Dis. 2017;9:45–53.[3]Mease Philip J, DD Gladman, A Ogdi et al. Treatment to Target in Psoriatic Arthritis with Apremilast: Probability of Achieving Targets and Comprehensive Control of Disease Manifestations. Arthritis Care & Research, 2020.Table 1.Disease characteristics in patients with PsA receiving APRPATIENTS WITH PsABasal, mean±SD6 Months, mean±SD12 Months, mean±SD18 Months, mean±SD“p” valueTJC3.3 ± 2.01.2 ± 2.31.1 ± 1.60.7 ± 1.1*p=0.002SJC2.4 ± 1.60.4 ± 0.91.0 ± 2.00.3 ± 1.0*p=0.001CRP6.8 ± 6.33.5 ± 3.83.4 ± 3.92.7 ± 4.1p=0.062DAPSA21.1 ± 5.65.6 ± 7.26.5 ± 8.52.9 ± 4.1*p=0.000MASES1 ± 1.40.1 ± 0.50 ± 00 ± 0p=0.16Table 2.Disease characteristics in patients with Psoriasis receiving APRPATIENTS WITH PSORIASISBasal, mean±SD6 Months, mean±SD12 Months, mean±SD18 Months, mean±SD“p” valuePASI9.5 ± 6.64.1 ± 4.72.2 ± 2.63.4 ± 3.8p=0.072Disclosure of Interests:None declared