Background/Purpose: 1) to evaluate clinical and subclinical markers of cardiovascular (CV) disease risk and its relationship with inflammation, disease activity and metabolic comorbidities in PsA patients and 2) to identify clinical and molecular profiles that could distinguish patients who may be benefit from the positive effects of PDE-4 inhibitor on CV risk.

Methods: Design: 1) Cross-sectional study including 100 PsA patients and 100 healthy donors (HDs) and 2) Longitudinal study including 45 patients treated with the PDE-4 inhibitor, Apremilast (n = 15), Methotrexate (MTX) (n = 15) alone or in combination (n = 15), evaluated at baseline and after 6 months of treatment. CV risk factors and clinical characteristics were recorded. Levels of 92 proteins mainly related to CV disease were evaluated in plasma by “Olink Proteomics” technology. The mRNA expression of CV-related proteins was analyzed in peripheral mononuclear cells (PBMCs). Cluster analyses were performed to identify specific clinical and molecular profiles of patients. ROC curve analyses were also performed to recognize biomarkers of disease activity, insulin resistance (IR) and therapeutic response.

Results: PsA patients showed a higher prevalence of metabolic alterations such as, obesity (30%) and IR (45%) compared to HDs. Metabolic complications were associated with disease activity and higher acute phase reactants. Specifically, IR state was related to a persistent inflammatory status (c-reactive protein) during the 5-years prior to this study. Thirty-six CV-related proteins were altered in the plasma of PsA patients and associated with clinical parameters such as disease activity, acute phase reactants, body surface area affected by psoriasis and the presence of onychopathy. Biomarkers of IR (MMP-3, CD-163 and FABP-4) and disease activity (GAL-3 and FABP-4) were identified by ROC analyses. Two clusters of PsA patients were identified depend on the clinical and molecular profiles which showed different therapeutic responses to Apremilast and MTX. Thus, the cluster 2 which included patients with higher prevalence of CV risk factors and increased CV-related proteins in plasma showed a better response with Apremilast compared to MTX. In these patients, PDE-4 inhibitor reduced disease activity in parallel with body mass index and IR state. Likewise, biomarkers of therapeutic response to Apremilast were recognized (CD-163, LTBR and CNTN-1) with high sensitivity and specificity.

Conclusion: 1) Metabolic alterations in PsA are associated with disease activity and persistence of inflammatory profile; 2) Subclinical CV risk biomarkers in PsA is related to clinical characteristics where CD-163 could play an important role; 3) PsA patients with a specific clinical and molecular profile showed better response to therapy with Apremilast and 4) circulating plasma levels of CD-163, LTBR and CNTN-1 could be useful as biomarkers of therapeutic response to Apremilast.

Funded by ISCIII (PI17/01316 and PI20/0079) co-financed by FEDER, and MINECO (RyC-2017-23437).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-molecular-profiles-determining-cardiovascular-risk-in-psoriatic-arthritis-specific-response-to-apremilast-and-methotrexate/