Article ; Online: Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches.
2019 Volume 28, Issue 7, Page(s) 756–768
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 ... ...
| 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. |
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| MeSH term(s) | Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Biological Products/therapeutic use ; Biomarkers/metabolism ; Clinical Trials as Topic ; Cytokines/metabolism ; Dermatitis, Atopic/immunology ; Dermatitis, Atopic/therapy ; Humans ; Immunity, Innate ; Immunosuppressive Agents/therapeutic use ; Interleukin-13/immunology ; Interleukin-4/immunology ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Quality of Life ; Skin/immunology ; Treatment Outcome |
| Chemical Substances | Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Biological Products ; Biomarkers ; Cytokines ; IL13 protein, human ; IL4 protein, human ; Immunosuppressive Agents ; Interleukin-13 ; Interleukin-4 (207137-56-2) ; dupilumab (420K487FSG) ; tralokinumab (GK1LYB375A) ; lebrikizumab (U9JLP7V031) |
| Language | English |
| Publishing date | 2019-04-15 |
| Publishing country | Denmark |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID | 1130936-2 |
| ISSN | 1600-0625 ; 0906-6705 |
| ISSN (online) | 1600-0625 |
| ISSN | 0906-6705 |
| DOI | 10.1111/exd.13911 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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