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Rapid Reduction in Staphylococcus aureus in Atopic Dermatitis Subjects Following Dupilumab Treatment.

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Rapid Reduction in Staphylococcus aureus in Atopic Dermatitis Subjects Following Dupilumab Treatment. The Journal of allergy and clinical immunology Simpson, E. L., Schlievert, P. M., Yoshida, T., Lussier, S., Boguniewicz, M., Hata, T., Fuxench, Z., De Benedetto, A., Ong, P. Y., Ko, J., Calatroni, A., Rudman Spergel, A. K., Plaut, M., Quataert, S. A., Kilgore, S. H., Peterson, L., Gill, A. L., David, G., Mosmann, T., Gill, S. R., Leung, D. Y., Beck, L. A. 2023

Abstract

Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities and Staphylococcus aureus skin colonization and infections. S. aureus 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 with dupilumab.Participants (n=71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple timepoints: S. aureus and virulence factor quantification, 16s rRNA microbiome, serum biomarkers, skin transcriptomic analyses and peripheral blood T-cell phenotyping.At baseline, 100% of participants were S. aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S. aureus after only 3 days (compared to placebo); 11 days before clinical improvement. Participants with the greatest S. aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S. aureus cytotoxins (day 7), perturbations in Th17 subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil and complement pathways (day 7) were also observed.Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S. aureus abundance in AD subjects, and this reduction correlates with reductions in the type 2 biomarker, CCL17 and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for Th17, neutrophils and complement activation as potential mechanisms to explain these findings.

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