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Review
. 2019 Jul;28(7):756-768.
doi: 10.1111/exd.13911. Epub 2019 Apr 15.

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Matthew Moyle  1 , Ferda Cevikbas  2 , Jamie L Harden  2 , Emma Guttman-Yassky  3
Affiliations
Review

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Matthew Moyle et al. Exp Dermatol. 2019 Jul.

Abstract

Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease-causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate-to-severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease-specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)-13 and IL-4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti-IL-4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate-to-severe AD. The anti-IL-13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL-13 epitopes with potentially different effects, are currently in advanced-stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine.

Keywords: atopic dermatitis; dupilumab; interleukin 13; interleukin 4; lebrikizumab; tralokinumab.

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Conflict of interest statement

MM is a consultant for Dermira. FC is an employee of Dermira. JLH is an employee of Dermira. EG is a consultant for AbbVie, Anacor, Celgene, Celsus Therapeutics, Dermira, Galderma, Glenmark, Janssen Biotech, LEO Pharmaceuticals MedImmune, Novartis, Pfizer, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, Vitae, Mitsubishi Tanabe, Eli Lilly, Asana Biosciences and Kiowa Kirin; is an investigator for Celgene, Glenmark, Leo Pharmaceuticals, MedImmune, Regeneron, Eli Lilly; is a member of advisory boards for Celgene, Celsus Therapeutics, Dermira, Galderma, Glenmark, MedImmune, Novartis, Pfizer, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, Vitae and Asana Biosciences.

Figures

Figure 1
Figure 1
Type 2 receptor for IL‐4 and IL‐13. (A) The interleukin‐4 type 2 receptor complex, comprised of IL‐4Rα and IL‐13Rα1 subunits. (B) Binding of IL‐4 to IL‐4Rα induces receptor dimerization with IL‐13Ra1 and signal transduction via the JAK/STAT pathway, leading to increased transcription of genes associated with inflammation. (C) In a similar way, binding of IL‐13 to IL‐13Rα1 also induces dimerization with IL‐4Ra, signal transduction and increased pro‐inflammatory gene expression. IL, interleukin; IL‐4Rα, IL‐4 receptor alpha; IL‐13Rα, IL‐13 receptor alpha
Figure 2
Figure 2
Mechanism of action for biologics targeting the IL‐4 and/or IL‐13 pathways. IL, interleukin; IL‐4Rα, IL‐4 receptor alpha; IL‐13Rα, IL‐13 receptor alpha
See this image and copyright information in PMC

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