Dupilumab therapy modulates circulating inflammatory mediators in patients with prurigo nodularis

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently approved for treatment of PN, but its effects on systemic inflammation are unknown. Thus, we aimed to characterize changes in plasma concentrations of inflammatory proteins following dupilumab treatment. In this exploratory study, plasma samples were collected from three patients with moderate-to-severe PN before and after ≥6 months of dupilumab. All patients exhibited clinically significant improvements post-treatment. Of the 2569 proteins tested, 186 were differentially expressed post-treatment (q<0.1, FC>1.3). Downregulated proteins included cytokines associated with Th1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), Th17/Th22 (IL-6, IL-22) signaling. Markers of innate immunity (IL-19, TLR1, NOS2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were also decreased (q<0.1). GSVA analysis of Th2, Th17, and Epithelial-Mesenchymal-Transition gene sets showed reduced pathway expression in the post-treatment cohort (p<0.05). Plasma cytokine levels of IL-11, NOS2, IL-13, IL-4, and IFNG (R2>0.75, q<0.10) showed the strongest correlations with pruritus severity. Dupilumab may reduce systemic inflammatory proteins associated with multiple immune and fibrosis pathways in PN patients, potentially modulating the development of systemic disease comorbidities.