1599 Rapid reduction in S. aureus in atopic dermatitis subjects following dupilumab treatment

Atopic dermatitis (AD) is characterized by type 2 inflammation, chronic pruritus and Staphylococcus aureus (SA) skin colonization and infections.SA is thought to play a role in AD severity.We characterized the changes in the host-microbial interface in AD subjects following type 2 blockade. Participants (N=71) with moderate-severe AD were enrolled in a RDBPC study (dupilumab vs placebo; 2:1) at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple timepoints: SA and virulence factor quantification, 16s rRNA microbiome, serum biomarkers, barrier function, skin transcriptomic analyses and PBMC phenotyping. Dupilumab treatment resulted in significant SA reductions after only 3 days; 11 days before clinical improvement. Those with the greatest SA reductions had the best clinical outcomes, and reductions correlated with CCL17 reductions. Reductions in SA cytotoxins (day 7), increases in skin-homing Th17 subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil and complement pathways (day 7) were also observed. Dupilumab very rapidly reduced SA abundance which correlated with reductions in the type 2 biomarker, CCL17. Immunoprofiling and transcriptomics suggest a role for Th17 immunity, while transcriptomic analysis also points to a role for neutrophil and complement activation as potential mechanisms to explain these findings.