Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches.
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.
['Moyle|Matthew|M|', 'Cevikbas|Ferda|F|', 'Harden|Jamie L|JL|', 'Guttman-Yassky|Emma|E|']
D000911:Antibodies, Monoclonal D061067:Antibodies, Monoclonal, Humanized D001688:Biological Products D015415:Biomarkers D002986:Clinical Trials as Topic D016207:Cytokines D003876:Dermatitis, Atopic D006801:Humans D007113:Immunity, Innate D007166:Immunosuppressive Agents D018793:Interleukin-13 D015847:Interleukin-4 D008214:Lymphocytes D011788:Quality of Life D012867:Skin D016896:Treatment Outcome
atopic dermatitis dupilumab lebrikizumab tralokinumab interleukin 13 interleukin 4