title: Drug evaluation review: dupilumab in atopic dermatitis.
abstract: Atopic dermatitis (AD) is characterized by type 2 helper T (Th2) cell-driven inflammation. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways. In Phase I and II studies of adults with moderate-to-severe AD, dupilumab administered as monotherapy or with topical corticosteroids resulted in rapid, significant improvements in clinical efficacy, patient-reported outcomes, and Th2-related serum and tissue biomarkers, and shifted the RNA expression profile of lesional skin to a more nonlesional signature. In all clinical studies to date, dupilumab has shown a favorable safety profile with no dose-limiting toxicity. The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.
authors.affiliation: Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Hamilton
authors.affiliation: Rockefeller University, Laboratory of Investigative Dermatology, 1230 York Ave, NY 10065, USA.|Center for Excellence in Eczema and Laboratory for Inflammatory Skin Diseases, Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai Medical Center, 1428 Madison Ave, NY 10029, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Rockefeller University, Laboratory of Investigative Dermatology, 1230 York Ave, NY 10065, USA.|Center for Excellence in Eczema and Laboratory for Inflammatory Skin Diseases, Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai Medical Center, 1428 Madison Ave, NY 10029, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000982:Antipruritics / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D004341:Drug Evaluation; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D011537:Pruritus / Q000188:drug therapy*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000982:Antipruritics; D016207:Cytokines; D018793:Interleukin-13; D015847:Interleukin-4; C582203:dupilumab
keywords: IL-13; IL-4; IL-4Rα; TARC; Th2; atopic dermatitis; dupilumab; efficacy; eotaxin-3; safety