IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis

Abstract

Dupilumab is a fully human antibody to interleukin-4 receptor a 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 a inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus.

The influence of treatment in alpine and moderate maritime climate on the composition of the skin microbiome in patients with difficult to treat atopic dermatitis

“…Previous studies show an effect of medication use on the skin microbiome. However, it was not possible to discontinue medication use in this group of patients with difficult to treat, moderate to severe disease . During this study, the use of medication was carefully monitored and showed no significant differences between both treatment groups.…”

“…However, it was not possible to discontinue medication use in this group of patients with difficult to treat, moderate to severe disease. 8,45 During this study, the use of medication was carefully monitored and showed no significant differences between both treatment groups. Results for patients using systemic medication at T0 did not deviate from the rest of the study population (data not shown).…”

A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review

“…It has been confirmed to be effective in patients with moderate to severe AD in several double-blind, placebocontrolled studies and in clinical practice [43][44][45]. The result showed that clinical improvement is positively correlated with increased favorable microbial community and reduced abundance of S. aureus [46]. More novel systemic immunomodulatory agents for AD are under development, and it is promising that these therapies will not only improve skin immunity but also adjust S. aureus colonization by modulating their cell wall proteins [19].…”

The skin microbiome as a clinical biomarker in atopic eczema: Promises, navigation, and pitfalls

“…Moreover, recent studies have shown S aureus levels to decrease during treatment of AD and to rebound after the end of treatment in some but not all patients. 8,9 Furthermore, we now have a better understanding of the mechanism behind the interaction between S aureus and other bacterial species, the skin barrier, and immune dysregulation in patients with AD. 10 Thus skin microbiome measurement of S aureus, notably a noninvasive procedure, might become a clinical biomarker for treatment success, most importantly indicating a sustained microbial response (SMR) that will allow determination of optimal treatment duration ( Fig 1).…”