Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with Staphylococcus aureus (SA) colonization. Dupilumab (DPL), an anti-IL-4Rα mAb that inhibits signaling of IL-4/IL-13, key drivers of Type 2/Th2 inflammation, is approved for patients aged ≥12 years in the USA with moderate-to-severe AD inadequately controlled by topical prescription treatments or when those therapies are not advisable, adult AD patients in Japan not adequately controlled with existing therapies, and adults with moderate-to-severe AD in Europe who are candidates for systemic therapy. We investigated DPL treatment in AD influences skin colonization by SA and skin microbiome diversity. In a phase 2 trial (NCT01979016), 54 adults with moderate-to-severe AD were randomized (1:1) to weekly subcutaneous injections with DPL 200mg or placebo (PBO) for 16 weeks. SA absolute abundance was assessed by qPCR and relative microbial composition by 16S rRNA sequencing. AD severity was assessed by the Eczema Area and Severity Index (EASI). Serum biomarkers (CCL17, CCL18, and IgE) were measured. At baseline, SA had higher absolute abundance on lesional vs non-lesional skin (P<0.05). Lesional skin showed a distinct cluster in microbial β-diversity (P<0.001) and lower α-diversity (P<0.05). DPL decreased SA absolute and relative abundance while overall microbial diversity increased. DPL improved EASI scores and decreased serum biomarkers. No major changes were noted with PBO. Improved EASI and serum biomarkers strongly correlated with decreased SA abundance (P<0.001). These results reveal strong links between SA, the skin microbial community, serum biomarkers, and AD severity, and demonstrate that targeted suppression of Type 2 immunity by anti-IL-4Rα mAb improves the skin microbial community.

Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Patients With Atopic Dermatitis