Systemic Therapies for Moderate-to-Severe Atopic Dermatitis: Expert Perspectives in Practice

February 2019 | Volume 18 | Issue 2 | Original Article | 122 | Copyright © 2019

Mark Lebwohl MD,a Andrew F. Alexis MD MPH,B Lisa A. Beck MD,c Julie K. Block BA,D Lawrence F. Eichenfield MD,E Luz Fonacier MD,f Emma Guttman-Yassky MD PhD,a Amy S. Paller MD MSc,g David Pariser MD FACP FAAD,h Jonathan I. Silverberg MD PhD MPH,i Mark Boguniewicz MD j

aDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY bDepartment of Dermatology, Skin of Color Center, Mount Sinai St. Luke's and Mount Sinai West, New York, NY cDepartment of Dermatology, University of Rochester Medical Center, Rochester, NY dNational Eczema Association, Novato, CA eDepartments of Dermatology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA fSection of Allergy and Clinical Immunology, Department of Medicine, NYU Winthrop-University Hospital, Mineola, NY gDepartments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL hDepartment of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA iDepartments of Dermatology, Preventive Medicine and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL jDivision of Allergy-Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, CO

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects around 13% of children and 7% of adults in the US. It can have a significant impact on the quality of life (QoL) of affected individuals due to pruritus and the visibility of lesions on the skin. AD is increasingly recognized as a systemic disease, since dysregulation of the adaptive and innate immune systems plays a key role in the underlying disease pathogenesis, which has important implications for how the condition is treated. Patients with moderate-to-severe disease who have failed to achieve disease control may benefit from systemic immunomodulatory treatments. Recently published expert perspectives outlined recommendations for the diagnosis and treatment of moderate-to-severe AD in adults, reflecting evidence-based, practical recommendations to support allergists and dermatologists in selecting appropriate treatment in the era of biologic therapies. To help clinicians understand how these practical recommendations can be implemented into clinical practice, we describe two real life case studies of adult patients with AD. In these case studies, we demonstrate how AD severity, treatment response, and treatment failure can be assessed, and the role of emerging systemic treatments in the management of moderate-to-severe AD. J Drugs Dermatol. 2019;18(2):122-129.

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INTRODUCTION

Atopic dermatitis (AD) is a chronic, relapsing, pruritic inflammatory skin disease that has an age-specific typical morphology and distribution.1 The prevalence of eczema is approximately 13% in US children2 and 7% in US adults.3,4 Incidence has increased by 2–3 fold during the past few decades in industrialized countries.5 AD commonly begins in childhood, with most childhood cases developing their first symptoms by age 6 years.6 The prevalence of AD is greater in black compared to white children in the US and a higher number of visits per capita for AD among US based Asians/Pacific Islanders and blacks has been reported. The development of long-term pigmentary alterations contributes to additional disease burden among patient populations with skin of color.7 Childhood AD may persist into adulthood in 20% to 50% of cases.8,9 However, adult-onset or recurrent AD also commonly occurs, with approximately 1 in 4 adults with AD reporting adult-onset of their AD worldwide.10 AD is associated with a high burden and significant impact on patient quality of life (QoL).4,11-13The pathophysiology of AD is complex, with interplay between environmental, genetic, and immunological factors, leading to dysfunction of the skin barrier and dysregulation of the immune system.1,14-17 AD is increasingly recognized as a systemic disease, since dysregulation of the adaptive and innate immune systems plays a key role in the underlying pathogenesis.18-22 This has important implications for how the condition is treated. AD is characterized by cutaneous and systemic inflammation,23 including T-cell activation and chronically activated memory B-cells.24,25 Furthermore, nonlesional skin in patients with moderate-to-severe disease shows abnormal immune and barrier abnormalities.18,22,26 AD is strongly associated with extracutaneous allergic disease, such as asthma, allergic rhi-

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