BackgroundAtopic dermatitis (AD) is a clinically heterogeneous immune-mediated skin disorder. The lack of reliable clinical stratification tools and predictive biomarkers for therapeutic response remains a critical unmet need to optimize treatment and advance precision dermatology.ObjectiveTo investigate the association between genetic variants and AD phenotypes and response to Dupilumab as a potential approach to individualize therapy in moderate-to-severe AD.Methods120 patients with moderate-to-severe AD treated with Dupilumab were enrolled at two Italian centers.
Clinical data, including phenotypes, severity, and comorbidities, were collected at baseline and after 48 weeks treatment with Dupilumab. Its efficacy was assessed as EASI75 and EASI90 achievements at week 48.
Genotyping of 521 SNPs was performed using next-generation sequencing (NGS). Cluster analysis and univariate logistic regression explored associations between genetic profiles and clinical variables.ResultsNGS-based genotyping enabled the stratification of patients into four distinct genetic clusters, each characterized by unique combinations of polymorphisms in skin barrier–related genes, namely FLG and KIF3A.
Specific SNPs in additional barrier-related genes (RPTN rs3001978, TH2LCRR rs2158177 and rs3091307) and Th2 pathway genes (IL4R rs1805016, STAT6 rs324011) were differentially distributed across the clusters.