Impact of CARD14 rs34367357 Mutation, Nutrition Status, and Seasonality on the Response to Biologic Therapy in Psoriasis—A Retrospective Observational Single-Center Study

<b>Background/Objectives:</b> Psoriasis is an immune-mediated disease influenced by genetic predisposition, environmental triggers, and metabolic comorbidities. Biologic therapies have markedly improved disease control; however, variability in patient response remains insufficiently understood. The aim of the study is to evaluate whether <i>CARD14</i> mutations and the season of treatment initiation influence the efficacy of biologic therapy in psoriasis. We also examined the potential interactions between <i>CARD14</i> status, seasonality, drug class, and nutrition status on short-term clinical outcomes. <b>Methods:</b> This retrospective study included 72 patients receiving biologic therapy within the Polish NHF B.47 program. Clinical endpoints (PASI, BSA, DLQI) were assessed at baseline and after 1, 4, 7, and 10 months. <i>CARD14</i> genotyping was performed using Sanger sequencing. Patients were stratified according to mutation status, season of therapy initiation (warm vs. cold), drug class, and BMI category. Statistical analyses included <i>t</i>-tests, chi-square, ANOVA, and MANOVA. <b>Results:</b> The <i>CARD14 rs34367357</i> mutation was associated with earlier disease onset (15.6 vs. 22.7 years, <i>p</i> = 0.0134) and higher DLQI baseline (<i>p</i> = 0.0265) but did not significantly impact treatment response. Therapy initiated during the warm season (April-September) led to greater PASI improvement (<i>p</i> < 0.0001). Obesity was associated with reduced response (<i>p</i> = 0.02385). Drug class and interaction effects were not statistically significant. <b>Conclusions:</b> Our findings suggest that seasonal timing, nutritional status, and genetic background may modulate the efficacy of biologic therapies in psoriasis. Although not statistically conclusive, the potential interaction between <i>CARD14 rs34367357</i> and seasonality warrants further investigation.