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

<jats:title>Abstract</jats:title><jats:p>Atopic dermatitis (<jats:styled-content style="fixed-case">AD</jats:styled-content>) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. <jats:styled-content style="fixed-case">AD</jats:styled-content> is associated with an increased risk of skin infections and a reduced quality of life. Most <jats:styled-content style="fixed-case">AD</jats:styled-content> 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 <jats:styled-content style="fixed-case">AD</jats:styled-content> pathobiology have made possible a new generation of more disease‐specific <jats:styled-content style="fixed-case">AD</jats:styled-content> therapies. <jats:styled-content style="fixed-case">AD</jats:styled-content> is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (<jats:styled-content style="fixed-case">ILC</jats:styled-content>2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (<jats:styled-content style="fixed-case">IL</jats:styled-content>)‐13 and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐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 <jats:styled-content style="fixed-case">AD</jats:styled-content>. In March 2017, dupilumab, a human anti–<jats:styled-content style="fixed-case">IL</jats:styled-content>‐4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate‐to‐severe <jats:styled-content style="fixed-case">AD</jats:styled-content>. The anti–<jats:styled-content style="fixed-case">IL</jats:styled-content>‐13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different <jats:styled-content style="fixed-case">IL</jats:styled-content>‐13 epitopes with potentially different effects, are currently in advanced‐stage trials. Here, we briefly review the underlying pathobiology of <jats:styled-content style="fixed-case">AD</jats:styled-content>, the scientific basis for current <jats:styled-content style="fixed-case">AD</jats:styled-content> targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance <jats:styled-content style="fixed-case">AD</jats:styled-content> therapy in the era of precision medicine.</jats:p>