Abstract
Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 191-202.e7 |
| Journal | Journal of Investigative Dermatology |
| Volume | 140 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2020 |
Funding
Outside of the submitted work, NT was an investigator for and has received research grants from Regeneron Pharmaceuticals, Inc.; RK was an scientific advisory board member and consultant for Janssen R&D LLC, Commense, Inc., and Prometheus Lab Inc.; MA, NMHG, and JH were employees and shareholders of Regeneron Pharmaceuticals, Inc.; TH and GP were employees of Sanofi and may hold stock and/or stock options in the company; EG was an investigator for AbbVie, Celgene, Eli Lilly and Company, GlaxoSmithKline, Regeneron Pharmaceuticals, Inc., Sanofi, Leo Pharma, Pfizer, Galderma, and Glenmark; served as a consultant for AbbVie, Anacor, Eli Lilly and Company, Galderma, GlaxoSmithKline, Leo Pharma, Menlo Therapeutics, Kiniksa, Pfizer, Realm, Regeneron Pharmaceuticals, Inc., Sanofi, Asana Biosciences, DBV, Kyowa, Daiichi Sankyo, Glenmark, Novartis, Dermira; and received research grants from Regeneron Pharmaceuticals, Inc., Sanofi, Pfizer, Galderma, Janssen, Celgene, Novartis, Dermira, AbbVie, Innovaderm, and Leo Pharma. RB was an investigator, consultant, advisory board member, speaker, and/or received honoraria from Antibiotx, Aquinox Pharma, Asana, Astellas, Brickell Biotech, Dermavant, Dermira, Dignity Sciences, Galderma, Glenmark, GSK-Stiefel, Hoffman-LaRoche Ltd., Kiniksa, Leo Pharma, Neokera, Pfizer, Regeneron Pharmaceuticals, Inc., Sienna Biopharmaceuticals, and Vitae Pharmaceuticals; and was a shareholder of Innovaderm Research; JIS was an investigator for AbbVie, Celgene, Chugai, Eli Lilly and Company, GlaxoSmithKline, Regeneron Pharmaceuticals, Inc., and Sanofi; a consultant for AbbVie, Anacor, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, Leo Pharma, Menlo, Kiniksa, Pfizer, Realm, Regeneron Pharmaceuticals, Inc., and Sanofi; and a speaker for Regeneron Pharmaceuticals, Inc., and Sanofi; JK was a consultant and recipient of research grants from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Dermira, Innovaderm, Janssen, Kadmon, Kyowa, Eli Lilly and Company, Merck, Novartis, Parexel, and Pfizer; was consultant and received personal fees from AbbVie, Baxter, Biogen Idec, Delenex, Kineta, Sanofi, Serono, and XenoPort; and was an investigator for Regeneron Pharmaceuticals, Inc.; AM served on the advisory board and was a consultant, investigator, and speaker and received grants and honoraria from AbbVie, Amgen, Janssen Biotech, Inc., and Leo Pharma; served on the advisory board and was a consultant and investigator and received grants and honoraria from Allergan; served on the advisory board and was an investigator and recipient of grants and honoraria from Boehringer Ingelheim; served as a consultant and investigator and was a recipient of grants and honoraria from Novartis, Pfizer, and XenoPort; was investigator and recipient of grants from Anacor, Celgene, Dermira, Merck, Neothetics, Regeneron Pharmaceuticals, Inc., and Symbio/Maruho; served on the advisory board, was an consultant and investigator, and received honoraria from Eli Lilly and Company; and was consultant and received honoraria from Galderma and Vitae Pharmaceuticals; RG was an investigator and recipient of research grants from Regeneron Pharmaceuticals, Inc.; had equity interest in and was co-founder and SAB of MatriSys Bioscience; had equity interest in and was SAB of Sente, Inc.; was a consultant for Roche; received a research grant from Novan; and received a research grant from Colgate Palmolive. The other authors state no conflict of interest. Research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. , ClinicalTrials.gov Identifier: NCT01979016 . Medical writing/editorial assistance was provided by Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. The authors thank Amnon Amir and Usman Chaudhry for their contributions to this study.
ASJC Scopus subject areas
- Dermatology
- Molecular Biology
- Biochemistry
- Cell Biology
