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      Drug Design, Development and Therapy (submit here)

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      Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy

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          Abstract

          Atopic dermatitis (AD) is among the most common inflammatory skin diseases in children and adults in industrialized countries. Up to one-third of adults (probably a smaller proportion in childhood) suffer from moderate-to-severe AD, whose recommended treatment is usually based on systemic therapies. The currently available therapeutics are limited, and AD management becomes challenging in most cases. Over the last few years, new advances in the understanding of AD pathogenic mechanisms and inflammatory pathways have led to the identification of specific therapeutic targets and new molecules have been tested. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that is able to block the signaling of both IL-4 and IL-13 and achieve rapid and significant improvements in adults with moderate-to-severe AD. Dupilumab is ready to inaugurate a long and promising biological target treatment option for Th2 cell-mediated atopic immune response that characterizes AD.

          Most cited references33

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          Atopic dermatitis: a disease of altered skin barrier and immune dysregulation.

          Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs. © 2011 John Wiley & Sons A/S.
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            Eczema prevalence in the United States: data from the 2003 National Survey of Children's Health.

            Using the 2003 National Survey of Children's Health sponsored by the federal Maternal and Child Health Bureau, we calculated prevalence estimates of eczema nationally and for each state among a nationally representative sample of 102,353 children 17 years of age and under. Our objective was to determine the national prevalence of eczema/atopic dermatitis in the US pediatric population and to further examine geographic and demographic associations previously reported in other countries. Overall, 10.7% of children were reported to have a diagnosis of eczema in the past 12 months. Prevalence ranged from 8.7 to 18.1% between states and districts, with the highest prevalence reported in many of the East Coast states, as well as in Nevada, Utah, and Idaho. After adjusting for confounders, metropolitan living was found to be a significant factor in predicting a higher disease prevalence with an odds ratio of 1.67 (95% confidence interval of 1.19-2.35, P=0.008). Black race (odds ratio 1.70, P=0.005) and education level in the household greater than high school (odds ratio 1.61, P=0.004) were also significantly associated with a higher prevalence of eczema. The wide range of prevalence suggests that social or environmental factors may influence disease expression.
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              Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches.

              Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus. Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental, and immunologic factors. These factors likely account for the heterogeneity of AD onset and the severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved through early interventions to protect the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention might improve long-term outcomes for AD and reduce the systemic allergen sensitization that leads to associated allergic diseases in the gastrointestinal and respiratory tract.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                15 May 2017
                : 11
                : 1473-1480
                Affiliations
                [1 ]Dermatology Unit, Livorno Hospital, Livorno
                [2 ]Dermatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
                Author notes
                Correspondence: Angelo Massimiliano D’Erme, Dermatology Unit, Livorno Hospital, Viale Alfieri, Livorno 57124, Italy, Tel +39 34 9845 1303, Email a.m.derme@ 123456gmail.com
                Article
                dddt-11-1473
                10.2147/DDDT.S113192
                5439982
                d48933dd-5420-48f2-9451-346b6e6c72e7
                © 2017 D’Erme et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
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                Pharmacology & Pharmaceutical medicine
                dupilumab,atopic dermatitis,eczema,il-4,il-13,biologics
                Pharmacology & Pharmaceutical medicine
                dupilumab, atopic dermatitis, eczema, il-4, il-13, biologics

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