Clinical Issues in Atopic Dermatitis by Integritas Communications

Debates & Discussions About Managing Moderateto-Severe Disease

This activity is provided by Integritas Communications. This activity is supported by an educational grant from Sanofi Genzyme and Regeneron Pharmaceuticals. This program is independent and is not part of the official AAD Annual Meeting, as planned by its Scientific Assembly Committee. This live activity will not offer continuing medical education (CME) credit.

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

AMY S. PALLER, MD

Chair, Department of Dermatology Director, Northwestern University Skin Disease Research Center Walter J. Hamlin Professor of Dermatology Professor of Dermatology and Pediatrics Feinberg School of Medicine Northwestern University Chicago, Illinois Dr. Amy Paller is the Walter J. Hamlin Professor and Chair of the Department of Dermatology and Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine. She also serves as Principal Investigator of the National Institutes of Health (NIH)-funded Skin Disease Research Center at Northwestern. An author of more than 400 original publications, Dr. Paller is an NIH-funded investigator who currently serves on the Council for the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Her laboratory focuses on topical delivery of gene therapy via nanotechnology, diabetic wound healing, and cutaneous innervation. Her major clinical interests are genetic skin disorders and pediatric cutaneous immunologic disorders, including atopic dermatitis. Dr. Paller has directed the Pediatric Dermatology Clinical Trials Unit at Northwestern University and the Lurie Children’s Hospital of Chicago for the past 20 years, and has been the lead investigator on several landmark trials. She has served on the Board of Directors of the American Academy of Dermatology, the Society for Investigative Dermatology, the Society for Pediatric Dermatology, the Women’s Dermatologic Society, the American Board of Dermatology, and the American Dermatological Association. She has been President of the Society for Pediatric Dermatology, Society for Investigative Dermatology, and the Women’s Dermatologic Society, and inaugural co-Chair of the Pediatric Dermatology Research Alliance. She is currently President of the International Eczema Council and the International Society of Pediatric Dermatology.

FACULTY

JONATHAN I. SILVERBERG, MD, PHD, MPH

Assistant Professor of Dermatology, Medical Social Sciences, and Preventive Medicine Department of Dermatology Feinberg School of Medicine Northwestern University Chicago, Illinois Dr. Jonathan Silverberg is an Assistant Professor of Dermatology, Medical Social Sciences, and Preventive Medicine at Northwestern Universityâ&#x20AC;&#x2122;s Feinberg School of Medicine. He is also founder and Director of Northwestern Medicine Multidisciplinary Eczema Center, and Director of the patch-testing clinic at Northwestern Memorial Hospital. Dr. Silverberg received his doctorate in neuroimmunology, medical degree, and master of public health degree in biostatistics and epidemiology from the State University of New York Downstate Medical Center in Brooklyn, where he also completed his internship in internal medicine. He completed his residency in dermatology at St. Lukeâ&#x20AC;&#x2122;s-Roosevelt Hospital Center and Beth Israel Medical Center in New York, New York. Dr. Silverbergâ&#x20AC;&#x2122;s area of clinical subspecialty is inflammatory skin disease, particularly atopic and contact dermatitis. He developed a multidisciplinary atopic dermatitis clinic that includes specialists in dermatology, allergy and immunology, neurology, and sleep medicine. An author of more than 300 peerreviewed articles, abstracts, books and book chapters, he has been a local and/ or national principal investigator for numerous clinical trials for novel treatments in atopic dermatitis and other inflammatory disorders. His research interests include dermatoepidemiology, health services research, patient-reported outcomes, comorbidities and the burden of inflammatory skin disease, and evidence-based dermatology. Dr. Silverberg has been recognized with several honors, including the Young Leadership Award from the American Dermatological Association in 2017, Teacher of the Year Award in the Department of Dermatology in 2015, Outstanding Teacher Award from the Feinberg School of Medicine in 2016, and the inaugural Georg Rajka Medal from the International Society of Atopic Dermatitis in 2014.

ERIC L. SIMPSON, MD, MCR FACULTY

Professor of Dermatology Director, Clinical Research Department of Dermatology Oregon Health & Science University Portland, Oregon

Dr. Eric Simpson is a Professor of Dermatology at Oregon Health & Science University.Â As Director of the Clinical Studies Unit, he is involved in clinical research funded by the National Institutes of Health and industry partners to study new approaches to chronic skin disease treatment and prevention. Dr. Simpson supports medical professional education and regularly instructs residents and medical students in dermatology. Additionally, he has published over 80 scientific articles in several high-impact peer-reviewed journals, including The New England Journal of Medicine and The Lancet. Recognized internationally, he has spoken about his approach to patient care and research at over 20 international conferences in Europe, North and South America, and Asia. Dr. Simpson volunteers in support of the National Eczema Association, where he serves as Co-Chair of the Scientific Advisory Committee. He also serves on the executive committee of Harmonizing Outcome Measures in Eczema (HOME)â&#x20AC;&#x201D;a group of patients, providers, and other stakeholders whose mission is to improve the quality of eczema research to better suit the needs of patients and policy makers. Dr. Simpson enjoys spending time with his wife and children, playing squash, camping, hiking, fishing, and biking.

TARGET AUDIENCE

The educational design of this activity addresses the needs of dermatologists, allergists/clinical immunologists, and other clinicians who treat patients with severe atopic dermatitis.

PREAMBLE

STATEMENT OF NEED/PROGRAM OVERVIEW

Atopic dermatitis is a common, chronic inflammatory disease that manifests primarily in the skin, although research has uncovered potential deleterious effects in other organ systems throughout the body.1,2 The multifactorial biopsychosocial burdens of atopic dermatitis often markedly reduce patientsâ&#x20AC;&#x2122; quality of life, particularly in those with moderate-to-severe disease.3,4 A better understanding of atopic dermatitis etiology has supported the development of new approaches to disease characterization and targeted therapies.5,6 Indeed, the first biologic medication is now available to treat patients with moderate-tosevere disease and several other agents are in late-stage clinical development.7 To best serve their patients with difficult-to-treat atopic dermatitis, dermatologists can benefit from updates on the latest clinical trial data and practical recommendations on how the growing evidence pool should be translated into daily clinical decision-making for patient assessment and treatment.7,8 In this Clinical Issuesâ&#x201E;˘ program, an expert faculty panel will discuss and debate the pathophysiologic underpinnings of atopic dermatitis, considerations related to comprehensively evaluating patients, and recommended therapeutic strategies for moderate-to-severe disease. Attendees are sure to leave this lively and engaging program with new information and a fresh perspective on the evolving best practices for managing patients with atopic dermatitis.

REFERENCES

1. Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015:66(suppl 1):8-16. 2. Brunner PM, et al. Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Invest Dermatol. 2017;137(1):18-25. 3. Whiteley J, et al. The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey. Curr Med Res Opin. 2016;32(10):1-7 [Epub ahead of print].

4. Drucker AM, et al. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol. 2017;137(1):26-30.

5. Mansouri Y, Guttman-Yassky E. Immune pathways in atopic dermatitis, and definition of biomarkers through broad and targeted therapeutics. J Clin Med. 2015;4(5):858-873. 6. Gandhi NA, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. 7. Simpson EL, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.

8. Ungar B, et al. An integrated model of atopic dermatitis biomarkers highlights the systemic nature of the disease. J Invest Dermatol. 2017;137(3):603-613.

Upon completion of this activity, participants will be better able to do the following: • Describe the pathophysiologic mechanisms and risk factors that contribute to atopic dermatitis development and persistence, with a focus on specific targets of current and emerging systemic treatments • Assess patients with atopic dermatitis over time for uncontrolled symptoms, sleep disturbances, comorbid conditions, and treatment responses • Describe the mechanistic rationales and clinical evidence for current and emerging biologic therapies in the treatment of moderate-to-severe atopic dermatitis • Individualize long-term therapeutic regimens for moderate-to-severe atopic dermatitis to prevent exacerbations, manage comorbidities, maximize healthrelated quality of life, and minimize treatment-related side effects • Communicate with patients and caregivers to improve their understanding of atopic dermatitis and the importance of treatment adherence and to promote shared decision-making

DISCLOSURE OF CONFLICTS OF INTEREST

It is the policy of Integritas Communications that all faculty, instructors, and planners disclose any real or apparent conflicts of interest relating to the topics of this educational activity. The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this activity: Amy S. Paller, MD Consultant/Advisor: Dermira, Inc., Eli Lilly and Company, Galderma Laboratories, L.P., Genentech, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC., Stiefel Laboratories, Inc., Valeant Pharmaceuticals International, Inc.; Grant/Research Support: LEO Pharma; Speakers Bureau: Laboratories Expanscience; Advisory Board: Menlo Therapeutics Inc., Pierre Fabre Laboratories, Inc., Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC. Jonathan I. Silverberg, MD, PhD, MPH Consultant/Advisor: AbbVie Inc., Eli Lilly and Company, Galderma Laboratories, GlaxoSmithKline, Kiniksa Pharmaceuticals Corp., LEO Pharma Inc., Menlo Therapeutics Inc., Pfizer Inc., Realm Therapeutics, Inc., Regeneron Pharmaceuticals, Inc. sanofi-aventis U.S. LLC., Science 37 Inc.; Grant/Research Support: GlaxoSmithKline; Speakers Bureau: Regeneron Pharmaceuticals, Inc. sanofi-aventis U.S. LLC.

PREAMBLE

EDUCATIONAL OBJECTIVES

Eric L. Simpson, MD, MCR Consultant/Advisor: AbbVie Inc., Eli Lilly and Company, Galderma Laboratories, L.P., LEO Pharma Inc., Menlo Therapeutics Inc., Pfizer Inc., Regeneron Pharmaceuticals, Inc., Sanofi Genzyme; Grant/Research Support: Eli Lilly and Company, GlaxoSmithKline, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc., Vanda Pharmaceuticals Inc.

PREAMBLE

Non-faculty

Rose O’Connor, PhD, CHCP; Jim Kappler, PhD; Sandy Breslow; Alison Kemp; and Bernard M. Abrams, MD, hereby state that neither they nor their spouses/ life partners have any financial relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

PROVIDER INFORMATION

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the providership of Integritas Communications.

DISCLOSURE OF UNLABELED USE

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. Integritas Communications, Sanofi Genzyme, and Regeneron Pharmaceuticals do not recommend the use of any agent outside of the labeled indications.

DISCLAIMER

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

SLIDES

GUIDELINES »»Guidelines of care for the management of atopic dermatitis: part 1. Diagnosis and assessment of atopic dermatitis. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410183/pdf/ nihms598033.pdf

»»Guidelines of care for the management of atopic dermatitis: part 2. Management and treatment of atopic dermatitis with topical therapies. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326095/pdf/ nihms598590.pdf

»»Guidelines of care for the management of atopic dermatitis: part 3. Management and treatment with phototherapy and systemic agents.

Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410179/pdf/ nihms-598620.pdf

»»Guidelines of care for the management of atopic dermatitis: part 4. Prevention of disease flares and use of adjunctive therapies and approaches. Sidbury R, et al. J Am Acad Dermatol. 2014;71(6):1218-1233. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430554/pdf/ nihms685688.pdf

PATIENT RESOURCES RESOURCE CENTER

»»International Eczema Council

Founded in late 2014, the International Eczema Council (IEC) is a global nonprofit organization led by dermatology experts on atopic dermatitis. The IEC is dedicated to increasing the understanding of atopic dermatitis and promoting its optimal management through research, education, and patient/family care. www.eczemacouncil.org

»»National Eczema Association

The National Eczema Association is a nonprofit organization founded in 1988 to improve the health and quality of life for individuals with eczema through research, support, and education. www.nationaleczema.org

CLINICAL ASSESSMENT TOOLS »»Eczema Area and Severity Index (EASI)

EASI is a clinician assessment tool designed to measure clinical severity of atopic dermatitis. Severity scores can range from 0 (clear) to 72 (very severe). Hanifin JM, et al. Exp Dermatol. 2001;10(1):11-18. http://www.homeforeczema.org/documents/easi-case-report-formfor-age-8-years-and-over.pdf

»»Investigator Global Assessment (IGA)

The IGA is a clinician assessment strategy designed to provide a snapshot of overall disease severity in dermatologic clinical trials. Futamura M, et al. J Am Acad Dermatol. 2016;74(2):288-294. https://www.ncbi.nlm.nih.gov/pubmed/26685719

»»Patient-Oriented Eczema Measure (POEM)

The POEM is a patient-administered measurement tool designed to assess occurrence and frequency of atopic dermatitis symptoms during the previous week through a simple 5-point scale, with a maximum total score of 28. Charman CR, et al. Arch Dermatol. 2004;140(12):1513-1519. https://jamanetwork.com/journals/jamadermatology/ fullarticle/480876 SCORAD is a clinical tool used to assess the extent and severity of eczema. Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31. http://adserver.sante.univ-nantes.fr/Compute.html

RESOURCE CENTER

»»Scoring Atopic Dermatitis (SCORAD)

SUGGESTED READING »»Management of difficult-to-treat atopic dermatitis.

Arkwright PD, et al. J Allergy Clin Immunol. 2013;1(2):142-151. www.pubmed.gov/24565453

»»Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Blauvelt A, et al. Lancet. 2017;389(10086):2287-2303. https://www.ncbi.nlm.nih.gov/pubmed/28478972

»»Dupilumab with concomitant topical corticosteroids in adult patients with atopic dermatitis who are not adequately controlled with or are intolerant to ciclosporin A, or when this treatment is medically inadvisable: a placebo-controlled, randomized phase 3 clinical trial (LIBERTY AD CAFÉ). de Bruin-Weller M, et al. Br J Dermatol. November 2017. [Epub ahead of print.] http://onlinelibrary.wiley.com/doi/10.1111/bjd.16156/epdf

»»Translating atopic dermatitis management guidelines into practice for primary care providers. Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565. http://pediatrics.aappublications.org/content/pediatrics/136/3/554.full.pdf

»»Persistence of mild to moderate atopic dermatitis.

RESOURCE CENTER

Margolis JS, et al. JAMA Dermatol. 2014;150(6):593-600. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352328/pdf/nihms665922.pdf

»»Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Narla S, Silverberg JI. Ann Allergy Asthma Immunol. 2018;120(1):66-72. http://www.annallergy.org/article/S1081-1206(17)31186-9/pdf

»»Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503. http://www.jaad.org/article/S0190-9622(16)30330-9/pdf

»»Serious complications from staphylococcal aureus in atopic dermatitis. Patel D, Jahnke MN. Ped Dermatol. 2015;32(6):792-796. www.pubmed.gov/26337792

»»Anti-interleukin-31 receptor A antibody for atopic dermatitis. Ruzicka T, et al. N Engl J Med. 2017;376(9):826-835. https://www.ncbi.nlm.nih.gov/pubmed/?term=28249150

»»Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. Simpson EL, et al. J Am Acad Dermatol. 2016;74(3):491-498. http://www.jaad.org/article/S0190-9622(15)02471-8/pdf

»»Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. Simpson EL, et al. N Engl J Med. 2016;375(24):2335-2348. www.pubmed.gov/27690741

»»Eczema and cardiovascular risk factors in 2 US adult population studies. Silverberg JI, Greenland P. J Allergy Clin Immunol. 2015;135(3):721-728. http://www.jacionline.org/article/S0091-6749(14)01677-7/pdf

»»The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey.

RESOURCE CENTER

Whiteley J, et al. Curr Med Res Opin. 2016;32(10):1645-1651. https://www.ncbi.nlm.nih.gov/pubmed/?term=27240604

NOTES 34

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