Biologics for Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has become a global health problem. The pathophysiology of AD includes both skin barrier and immune abnormalities, with type 2 immune deviation central to several clinical phenotypes and underlying endotypes. Recognition of the persistent nature and systemic aspects of AD provides a rationale for treatment with a biologic. Dupilumab has been approved for patients 6 years of age and older with moderate to severe AD. Monoclonal antibodies are in phase 3 trials and may become part of a precision medicine approach to AD.

Boguniewicz M 《-》

Current and Emerging Biologics for Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic pruritic inflammatory skin disease that affects all ages and is recognized as a global health problem. Pathophysiology is complex with skin barrier abnormalities, immune dysregulation, and microbial dysbiosis all implicated. Markers of immune and inflammatory activation in the circulation provide a rationale for systemic therapy. Type 2 immune polarization is central, though other cytokine pathways including Th22 and Th17/IL-23 have been described, suggesting additional therapeutic targets in a subset of patients. Dupilumab and tralokinumab are monoclonal antibodies currently approved for moderate-to-severe AD with lebrikizumab and nemolizumab in late stages of development.

Nevid M ，Boguniewicz M 《-》

The Role of Interleukins 4 and/or 13 in the Pathophysiology and Treatment of Atopic Dermatitis.

Moderate to severe atopic dermatitis (AD) can be debilitating and often requires use of systemic immunosuppressant therapy to achieve adequate disease control. There are currently no US Food and Drug Administration-approved systemic agents for the long-term treatment of AD. Recent insight has identified the T helper 2 cytokines, interleukins 4 and 13, as playing a major role in the pathogenesis of AD. There are multiple novel biologic agents in development that target interleukins 4 and/or 13 for the treatment of moderate to severe AD. The age of targeted biologics for AD has arrived.

Silverberg JI ，Kantor R 《-》

Dupilumab for the treatment of adolescents with atopic dermatitis.

Senner S ，Seegräber M ，Frey S ，Kendziora B ，Eicher L ，Wollenberg A ... -  《-》

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 M ，Cevikbas F ，Harden JL ，Guttman-Yassky E ... -  《-》