Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment.

Abstract

BACKGROUND:

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.

OBJECTIVES:

This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab.

METHODS:

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 time points: S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping.

RESULTS:

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), which was 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-cell subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil, and complement pathways (day 7) were also observed.

CONCLUSIONS:

Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, 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 cells, neutrophils, and complement activation as potential mechanisms to explain these findings.

• Authors: Eric L Simpson, Patrick M Schlievert, Takeshi Yoshida, Stephanie Lussier, Mark Boguniewicz, Tissa Hata, Zelma Fuxench, Anna De Benedetto, Peck Y Ong, Justin Ko, Agustin Calatroni, Amanda K Rudman Spergel, Marshall Plaut, Sally A Quataert, Samuel H Kilgore, Liam Peterson, Ann L Gill, Gloria David, Tim Mosmann, Steven R Gill, Donald Y M Leung, Lisa A Beck
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 152 Issue 5 Pg. 1179-1195 (11 2023) ISSN: 1097-6825 [Electronic] United States
• PMID: 37315812 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• dupilumab
• Antibodies, Monoclonal, Humanized

Topics

• Humans
• Dermatitis, Atopic (genetics)
• Staphylococcus aureus
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Skin (metabolism)
• Staphylococcal Infections (drug therapy)
• Severity of Illness Index
• Treatment Outcome