Methotrexate Exposure and Inflammatory–Metabolic Biomarker Networks in Hospitalized Patients with Psoriasis: A Network Analysis Approach

Background: Psoriasis is a chronic immune-mediated inflammatory disorder strongly associated with cardiometabolic comorbidities. Although methotrexate (MTX) is widely used for moderate-to-severe disease, its influence on the relationships between inflammatory and metabolic biomarkers remains insufficiently characterized. Methods: This retrospective observational study included 132 hospitalized adult patients with psoriasis, stratified into untreated (n = 101) and MTX-treated (n = 31) groups. Inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), and metabolic indices, triglyceride–glucose index (TyG), metabolic score for insulin resistance (METS-IR), and atherogenic index of plasma (AIP), were analyzed. Group comparisons were performed using Mann–Whitney U and χ2 tests. Spearman correlation matrices and regularized partial correlation networks (EBICglasso, γ = 0.5) were constructed separately for each group to explore inflammatory–metabolic connectivity. Results: MTX-treated patients exhibited lower NLR (p = 0.035) and fasting glucose levels (p = 0.004), while CRP, ESR, and composite metabolic indices did not differ significantly. In untreated patients, correlation analysis showed multiple significant cross-domain associations between inflammatory and metabolic markers. In contrast, fewer such associations reached statistical significance in the MTX-treated group. Network analysis indicated a less densely connected structure in the MTX group (9 vs. 12 non-zero edges); however, formal network comparison did not identify statistically significant differences between groups. Conclusions: Although fewer statistically significant cross-domain correlations were observed in MTX-treated patients, no statistically significant differences in network structure were detected between groups. These findings are exploratory and hypothesis-generating, not indicative of methotrexate-related modification of network structure, and are limited by the small size of the MTX-treated subgroup.