Dupilumab significantly improves skin barrier function in patients with moderate‐to‐severe atopic dermatitis

Abstract

Background Atopic dermatitis (AD) is characterized by abnormal skin lipids that are largely driven by hyperactivated type 2 immune responses. The antibody to the α‐subunit of interleukin (IL)‐4 receptor, dupilumab, was recently approved to treat AD and demonstrated strong efficacy. However, the role of dupilumab therapy in the regulation of skin barrier structure and function has not been fully explored. Methods We have evaluated the content of lipids and transepidermal water loss (TEWL) in lesional and non‐lesional skin of adults and adolescents with moderate‐to‐severe AD over the course of 16‐week treatment with dupilumab and compared those values with that of matched healthy volunteers. Results Dupilumab treatment provided a significant decrease in TEWL in AD lesions, lowering it almost to the levels seen in the skin of healthy subjects. Blocking IL‐4/IL‐13 signaling with dupilumab normalized lipid composition (decreased levels of ceramides with non‐hydroxy fatty acids and C18‐sphingosine and increased the level of esterified omega‐hydroxy fatty acid‐containing ceramides) and increased ceramide chain length in lesional as well as non‐lesional stratum corneum of AD patients. Partial changes for these parameters were already observed after 2 weeks, with a full response achieved after 8 weeks of dupilumab treatment. Conclusions Inhibition of IL‐4/IL‐13 signaling by dupilumab allows restoration of skin lipid composition and barrier function in patients with moderate‐to‐severe AD.

Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate‐to‐severe atopic dermatitis

“…16 Multiple studies have shown that dupilumab treatment leads to clinical improvements 17 along with reductions of inflammatory cell infiltrates and proinflammatory cytokine and chemokine expression in lesions 18 and an enhanced skin barrier function with decreased transepidermal water loss (TEWL) and normalized epidermal lipid composition. [19][20][21][22][23][24] Likewise, an increased microbial diversity and decrease of S. aureus abundance during dupilumab treatment was reported. 25 Moreover, clinical signs of skin infections (mostly caused by S. aureus) were less frequent in dupilumab treated patients as compared to controls in prospective placebo-controlled studies.…”

Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-κB and JAK2/STAT3 in HaCaT Human Keratinocytes

“…JAK/STAT pathway regulates the major signaling cascades for many cytokines, chemokines and growth factors, and it also participates in intracellular signal transduction and expression [ 21 ]. As shown in Figure 5 A,B, when cells were co-treated with TNF-α and IFN-γ, compound 1 significantly downregulated the phosphorylation of JAK2 and STAT3.…”

New Concepts in Barrier Dysfunction in CRSwNP and Emerging Roles of Tezepelumab and Dupilumab

“…23,24 Dupilumab treatment of patients with AD resulted in restoration of skin barrier function by restoring skin lipid composition subsequently decreasing transepidermal water loss. 25,26 The rapid ability of dupilumab to improve sense of smell was investigated further in a transgenic mouse model with IL-13 specifically expressed within the olfactory epithelium. 27 Neuronal loss was seen associated with inflammatory infiltration by macrophages and increased expression of a mucin gene, MUC5AC, and eosinophil chemokines although eosinophil levels were unexpectedly low.…”

“…23,24 Dupilumab treatment of patients with AD resulted in restoration of skin barrier function by restoring skin lipid composition subsequently decreasing transepidermal water loss. 25,26…”