Therapeutic pipeline for atopic dermatitis: End ofTherapeutic pipeline for atopic dermatitis: End ofthe drought?
Amy S. Paller, MS, MD,a Kenji Kabashima, MD, PhD,b and Thomas Bieber, MD, PhD, MDRAc
INTRODUCTION
Until the past year, our therapeutic armamentarium forUntil the past year, our therapeutic armamentarium fortreating atopic dermatitis (AD) was still primarily topicalcorticosteroids and, for more severe disease, systemicimmunosuppressants. The pipeline of more targeted topicaland systemic therapies is expanding based on our growingunderstanding of the mechanism for AD and is particularlyfocused on suppressing the skewed immune activation. Mostagents are in phase 2 clinical trials. Crisaborole, a topicalphosphodiesterase 4 (PDE4) inhibitor, became available in late2016 in the United States for mild-to-moderate AD, with otherPDE4 inhibitors, an agonist of the aryl hydrocarbon receptor,Janus kinase inhibitors, and commensal organisms also intrials for topical application. The first highly effective mAb forAD, dupilumab, targets the IL-4/IL-13 receptor and wasapproved in early 2017 in the United States for moderate-tosevereadult AD. Other biologics similarly inhibit TH2cytokines (thymic stromal lymphopoietin, IL-4, IL-5, IL-13,and the itch-specific cytokine IL-31 and their receptors) orTH22/TH17 cytokines, levels of which are increased in lesionalskin. Orally administered small-molecule inhibitors thatsuppress inflammation (targeting chemoattractant receptor–homologous molecules expressed on TH2 lymphocytes, PDE4,the histamine 4 receptor, and Janus kinase) or specificallyitching (eg, NK1R inhibitors) are also being studied.Comparing biomarkers with individual responses toexperimental agents will help to determine subphenotypesINFORMATION FOR CATEGORY 1 CME CREDITCredit can now be obtained, free for a limited time, by reading the reviewarticles in this issue. Please note the following instructions.Method ofPhysicianParticipationin Learning Process:Thecorematerialfor these activities can be read in this issue of the Journal or online at the JACIWeb site: www.jacionline.org. The accompanying tests may only be submittedonline at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: September 2017. Credit may be obtained forthese courses until August 31, 2018.Copyright Statement: Copyright 2017-2018. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects ofallergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergicdisease.Accreditation/Provider Statements and Credit Designation: TheAmerican Academy of Allergy, Asthma & Immunology (AAAAI) isaccredited by the Accreditation Council for Continuing Medical Education(ACCME) to provide continuing medical education for physicians.The AAAAI designates this journal-based CME activity for a maximum of1.00 AMA PRA Category 1 Credit. Physicians should claim only the creditcommensurate with the extent of their participation in the activity.List of Design Committee Members: Amy S. Paller, MS, MD, KenjiKabashima, MD, PhD, and Thomas Bieber, MD, PhD, MDRA (authors);Stephan Weidinger, MD, PhD (editor)Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: A. S. Paller has consultant arrangementswith Dermira, Eli Lilly, Galderma, GlaxoSmithKline-Stiefel, Novartis,Pfizer, Regeneron/Sanofi, Roivant, and Valeant and has receivedgrants from AbbVie, Celgene, LEO, and Novartis. K. Kabashima hasconsultant arrangements with Chugai and Maruho and has received grantsfrom Japan Tobacco. T. Bieber has consultant arrangements with Astellas,Sanofi/Regeneron, Pfizer, Novartis, Lilly, Galderma, Roivant, Menlo TX,GlaxoSmithKline, and Daiichi-Sankyo; has received payment for lecturesincluding Astellas, Pfizer and Sanofi; and has received payment for manuscriptpreparation from Sanofi/Regeneron. S. Weidinger disclosed no relevantfinancial relationships.Activity Objectives:1. To be able to name several targets of pharmacologic and biologicdrugs in development for atopic dermatitis (AD) in the pathwaysof inflammation.2. To know the mechanism of action of recently approved pharmacologicand biologic drugs for AD.3. To describe the main differences in the cutaneous microbiome betweenAD skin and normal skin.Recognition of Commercial Support: This CME activity has notreceived external commercial support.List of CME Exam Authors: Niha Qamar, MD, Samantha R. Swain,MD, and Suzanne S. Teuber, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevantfinancial relationships.From athe Departments of Dermatology and Pediatrics, Northwestern University FeinbergSchool of Medicine, Chicago; bthe Department of Dermatology,Kyoto UniversityGraduate School of Medicine, and the Singapore Immunology Network (SIgN) andInstitute of Medical Biology, Agency for Science, Technology and Research(A*STAR), Biopolis; and cthe Department of Dermatology and Allergy, Universityof Bonn, and the Christine K€uhne-Center for Allergy Research and Education, Davos.Received for publication May 29, 2017; revised July 22, 2017; accepted for publicationJuly 25, 2017.Corresponding author: Amy S. Paller, MS, MD, Department of Dermatology, NorthwesternUniversity Feinberg School of Medicine, 676 North St Clair St, Suite 1600,Chicago, IL 60611. E-mail: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo. CrossMark symbol notifies online readers when updates have been made to thearticle such as errata or minor corrections0091-6749/$36.00 2017 American Academy of Allergy, Asthma & Immunologyhttp://dx.doi.org/10.1016/j.jaci.2017.07.006633within AD that predict prognosis and treatment responses. (JAllergy Clin Immunol 2017;140:633-43.)
