*Study Group*

This prospective cohort study was conducted in 34 patients (27 men and seven women) with plaque psoriasis (age: 30–73 years) and eight healthy volunteers (age: 30–57 years) as the control group. The study was approved by the Bioethics Commission at the University of Warmia and Mazury in Olsztyn, Poland (Resolution 16/2019). Each patient included in the study provided informed consent for participation. The inclusion criteria included being of an age higher than 18 years and a diagnosis of moderate-to-severe plaque psoriasis. The exclusion criteria were as follows: age below 18 years, mild plaque psoriasis, pregnancy, breastfeeding, and previous biological treatment (in the case of patients who qualified for MTX treatment). Due to the requirements of the treatment program for moderate-to-severe plaque psoriasis in Poland, patients starting ADA treatment confirmed the contraindications and/or side effects associated with the use of at least two classic methods of systemic psoriasis treatment or a history of ineffective systemic treatment. The systemic treatment is understood as the use of at least two of the following agents: MTX, cyclosporine, acitretin, and psoralen ultraviolet A (PUVA).

Of the patients, 17 were treated only with MTX and the remaining 17 were treated with ADA only. The patients received oral MTX at a dose of 7.5–20 mg per week and subcutaneous ADA at an initial dose of 80 mg followed by 40 mg every 2 weeks. The observation period lasted 12 weeks. The following parameters were evaluated for each subject: body mass index (BMI), the severity of psoriasis based on the Psoriasis Area and Severity Index (PASI), and body surface area (BSA). Depending on risk factors, such as age, sex, systolic blood pressure, smoking, and total cholesterol, the risk of fatal cardiovascular disease events over the next 10-year period was estimated using SCORE charts [16]. Laboratory tests to determine E-selectin and VCAM-1 serum levels were performed via an enzyme-linked immunosorbent assay (commercial ELISA kit, EIAab Science Co., Ltd., Wuhan, China) by using fasting blood samples obtained before and after 12 weeks of treatment.

Statistical analyses were performed using Statistica 13.1 (StatSoft Poland). Mean values and standard deviations (±SD) were used to describe the level of variables (PASI, BSA, VCAM-1, E-selectin) and demographic characteristics of the studied groups. The distributions of all studied explanatory metric variables in the groups were compared to the normal distribution using the Shapiro–Wilk

test, and the homogeneity of variance was tested using the Bartlett test. The one-way ANOVA model was used when the important assumptions for the analysis of variance were met. In case of failure to meet the assumption with a distribution close to normal, the Kruskal–Wallis test was used. The Mann–Whitney test was used to test the differentiation of variable levels between two groups: MTX vs. control and ADA vs. control. Comparisons of variables over time (baseline (W0) vs. the end of the study (W12)) were made using the paired samples Student's T-test if a parametric analysis was possible. For other cases, the nonparametric Wilcoxon test was used. Correlations were analyzed using Spearman's correlation coefficient. The χ<sup>2</sup> test was used to compare the distribution of two demographic nominal characteristics (sex, smoking) between the experimental and control groups. The Kruskal–Wallis test was also used for the comparison of the level of VCAM-1 and E-selectin between four groups of patients classified as presenting different SCORE risk levels. Differences and correlations were considered statistically significant at *p* < 0.05.
