Marching Forward in Atopic Dermatitis

This activity is provided by Integritas Communications.

This activity is supported by a grant from Sanofi Genzyme and Regeneron Pharmaceuticals.

The Non-CME Corporate Forum content and views expressed therein do not necessarily reflect the views, policies, or position of the American College of Allergy, Asthma & Immunology.

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FACULTY FACULTY

Peter A. Lio, MD

Clinical Assistant Professor of Dermatology and Pediatrics Feinberg School of Medicine Northwestern University Director, Chicago Integrative Eczema Center Founding Partner, Medical Dermatology Associates of Chicago Chicago, Illinois

Dr. Peter Lio is a Clinical Assistant Professor of Dermatology and Pediatrics at Northwestern University Feinberg School of Medicine.

Dr. Lio received his medical degree from Harvard Medical School, Boston, Massachusetts, and completed his internship in Pediatrics at Boston Children’s Hospital and his dermatology training at Harvard, where he served as Chief Resident in Dermatology. While at Harvard, he received formal training in acupuncture. Dr. Lio is the founding director of the Chicago Integrative Eczema Center, and currently serves as a board member and scientific advisory committee member for the National Eczema Association. He has over 100 publications in the peer-reviewed literature.

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Anne Marie Singh, MD FACULTY

Associate Professor of Pediatrics Director, Food Allergy Research and Education Center of Excellence University of Wisconsin School of Medicine & Public Health Madison, Wisconsin

Dr. Anne Marie Singh is an Associate Professor of Pediatrics in the Division of Allergy, Immunology and Rheumatology, a Food Research Institute Affiliate, and the Director of the Food Allergy Research and Education Center of Excellence at the University of Wisconsin-Madison.

After completing her allergy-immunology fellowship and post-doctoral training at the University of Wisconsin-Madison, Dr. Singh joined the faculty at Northwestern University Feinberg School of Medicine for 8 years, returning to the University of Wisconsin in 2017. Her research program is focused on atopic dermatitis and food allergy, including studies to advance clinical care, as well as mechanistic studies on how environmental and microbial exposures affect disease. She performs translational and clinical studies to better understand food allergy, atopic dermatitis, and early life wheezing.

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TARGET AUDIENCE The overall design of this activity addresses the needs of allergists/ clinical immunologists and other clinicians who treat patients with moderate-to-severe atopic dermatitis.

Upon completion of this activity, participants will be better able to do the following: • Discuss clinically relevant pathophysiologic processes in atopic dermatitis • Evaluate patients with moderate-to-severe atopic dermatitis for disease severity, comorbid conditions, and other biopsychosocial consequences • Describe the clinical profiles and prescribing considerations for targeted therapies for atopic dermatitis • Tailor therapy regimens for patients with moderate-to-severe atopic dermatitis based on ongoing symptoms, burdens, comorbidities, and shared clinical decision-making

PROGRAM AGENDA

7:00 pm–7:30 pm Registration and Dinner 7:30 pm–7:40 pm Preactivity Questionnaire and Faculty Introductions 7:40 pm–7:55 pm Atopic Dermatitis Pathophysiology 7:55 pm–8:15 pm Clinical Characteristics and Patient Assessment 8:15 pm–8:30 pm Personalizing Therapy for Patients With Moderateto-Severe Atopic Dermatitis 8:30 pm–8:45 pm Choose-a-Case™ 8:45 pm–9:00 pm Postactivity Questionnaire and Question & Answer

STATEMENT OF NEED/PROGRAM OVERVIEW Atopic dermatitis is a common, chronic inflammatory disease that manifests primarily in the skin, although research has uncovered potentially deleterious effects in other organ systems throughout the body.1,2 The disease-related physical and biopsychosocial burdens of this condition can have a substantial effect on patient and parent/caregiver quality of life. 3,4 Furthermore, people with atopic dermatitis have a higher likelihood of developing atopic comorbidities, also known as the atopic march. 5 A better understanding of atopic dermatitis disease

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LEARNING OBJECTIVES

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etiology has resulted in new insights into disease characterization and led to the development of targeted therapies.6-8 As a result, the first biologic therapy is now FDA-approved to treat both adolescent and adult patients with moderate-to-severe atopic dermatitis, with other novel therapies in late-stage clinical development.8-11 In this Interactive Exchange™ program, two experts in atopic dermatitis will review the pathophysiologic underpinnings of atopic dermatitis, new insights into disease characterization (including emerging research in distinct phenotypes and endotypes), common atopic and nonatopic comorbidities, and recommended management strategies for adolescents and adults with more severe disease. 5,12-15 In the final segment of the program, attendees will select a case study for discussion, giving the faculty an opportunity to summarize the newly presented information in the context of a practical, real-world scenario.

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. Carroll CL, et al. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005;22(3):192-199.

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. Paller AS, et al. The atopic march and atopic multimorbidity: many trajectories, many pathways. J Allergy Clin Immunol. 2019;143(1):46-55.

6. 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.

7. Gandhi NA, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.

8. Renert-Yuval Y, Guttman-Yassky E. What’s new in atopic dermatitis. Dermatol Clin.

2019;37(2):205-213.

9. Wollenberg A, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019;143(1):135-141.

10. Simpson EL, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.

N Engl J Med. 2016;375(24):2335-2348.

11. Simpson EL, et al. Dupilumab efficacy and safety in adolescents with moderate-tosevere atopic dermatitis: results from a multicenter, randomized, placebo-controlled, double-blind, parallel-group, phase 3 study. Presented at the 27th EADV Congress; September 12-16, 2018; Paris, France. Poster 4640.

12. Czarnowicki T, et al. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019;143(1):1-11.

13. Sandhu JK, et al. Association between atopic dermatitis and suicidality: a systemic review and meta-analysis. JAMA Dermatol. 2019;155(2):178-187.

14. Brunner PM, et al. Increasing comorbidities suggset that atopic dermatitis is a systemic disorder. J Invest Dermatol. 2017;137(1):18-25.

15. AriĂŤns LFM, et al. Dupilumab in atopic dermatitis: rationale, latest evidence and place in therapy. Ther Adv Chronic Dis. 2018;9(9):159-170.

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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.

Peter A. Lio, MD Consultant/Independent Contractor: Abbvie Inc., Altus Labs, LLC, AOBiome, Dermavant Sciences, Inc., Eli Lilly and Company, Galderma Laboratories, L.P., IntraDerm Pharmaceuticals, Johnson & Johnson, Kiniksa Pharmaceuticals, Ltd., La Roche-Posay, Menlo Therapeutics Inc., Micreos BV, Pfizer Inc., Pierre Fabre Laboratories, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Theraplex, UCB Biopharma, Unilever; Grant/Research Support: Abbvie Inc., AOBiome, The Atopic Dermatitis Foundation, Regeneron Pharmaceuticals, Inc.; Honoraria: Abbvie Inc., Altus Labs, LLC, AOBiome, Dermavant Sciences, Inc., Eli Lilly and Company, Galderma Laboratories, L.P., IntraDerm Pharmaceuticals, Johnson & Johnson, Kiniksa Pharmaceuticals, Ltd., La Roche-Posay, Menlo Therapeutics Inc., Micreos BV, Pfizer Inc., Pierre Fabre Laboratories, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Theraplex, UCB Biopharma, Unilever; Speakers Bureau: La Roche-Posay, Pfizer Inc., Pierre Fabre Laboratories, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme; Stock Shareholder: Altus Labs, LLC, Franklin Bioscience, Micreos BV, Syncere Skin Systems, Theraplex Anne Marie Singh, MD Grant/Research Support: Food Allergy Research and Education; National Institutes of Health

Nonfaculty Jim Kappler, PhD; Rose O’Connor, PhD, CHCP; and Stacey Ullman, MHS, 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 STATEMENT 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 providership of Integritas Communications.

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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:

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 and Sanofi Genzyme and Regeneron Pharmaceuticals do not recommend the use of any agent outside of the labeled indications.

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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 patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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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

» Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

Wollenberg A, et al. J Eur Acad Dermatol Venereol. 2018;32(5):657-682.

RESOURCE CENTER

https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.14891

» Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

Wollenberg A, et al. J Eur Acad Dermatol Venereol. 2018;32(6):850-878. https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.14888

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PATIENT RESOURCES » 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. http://www.eczemacouncil.org/for-patients/

» 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. http://www.nationaleczema.org

CLINICAL ASSESSMENT TOOLS » Children’s Dermatology Life Quality Index (CDLQI)

CDLQI is 10-question patient-reported assessment tool designed to measure impact of any skin disease on the lives of children ages 4-16.

Lewis-Jones MS, Finlay AY. Br J Dermatol. 1995;132(6):942-949. https://www.cardiff.ac.uk/medicine/resources/quality-of-life-questionnaires/ childrens-dermatology-life-quality-index

» Eczema Area and Severity Index (EASI)

http://www.homeforeczema.org/documents/easi-case-report-form-for-age-8years-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. http://www.pubmed.gov/26685719

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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.

» Patient-Oriented Eczema Measure (POEM)

The POEM is a patient-oriented, self-assessed measurement tool for monitoring aspects of atopic dermatitis in routine clinical practice or in the clinical trial setting.

Charman CR, et al. Arch Dermatol. 2004;140(12):1513-1519. https://www.nottingham.ac.uk/research/groups/cebd/resources/poem.aspx

» Scoring Atopic Dermatitis (SCORAD)

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

SUGGESTED READING Atopic Dermatitis Overview and Pathogenesis » Atopic dermatitis endotypes and implications for targeted therapeutics.

Czarnowicki T, et al. J Allergy Clin Immunol. 2019;143(1):1-11.

https://www.jacionline.org/article/S0091-6749(18)31572-0/fulltext

» Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

Paternoster L, et al. J Allergy Clin Immunol. 2018:141(3):964-971.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840507/?report=reader

» Pathogenesis of atopic dermatitis.

RESOURCE CENTER

Peng W, Novak N. Clin Exp Allergy. 2015;45(3):566-574. https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.12495

» Expression patterns of atopic eczema and respiratory illnesses in a high-risk birth cohort.

Singh AM, et al. J Allergy Clin Immunol. 2010:125(2):491-493. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967254/

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Patient Burden and Comorbidities » Determinants of disease severity among patients with atopic dermatitis: association with components of the atopic march.

Holm JG, et al. Arch Dermatol Res. 2019;311(3):173-182.

https://link.springer.com/article/10.1007%2Fs00403-019-01895-z

» The atopic march and atopic multimorbidity: many trajectories, many pathways.

Paller AS, et al. J Allergy Clin Immunol. 2019;143(1):46-55.

https://www.jacionline.org/article/S0091-6749(18)31638-5/fulltext

» Association between atopic dermatitis and suicidality: a systematic review and meta-analysis Sandhu JK, et al. JAMA Dermatol. 2019;155(2):178-187.

https://jamanetwork.com/journals/jamadermatology/article-abstract/2717582

» Association of atopic dermatitis with allergic, autoimmune, and cardiovascular comorbidities in US adults.

Silverberg JI, et al. Ann Allergy Asthma Immunol. 2018;121(5):604-612 https://www.ncbi.nlm.nih.gov/pubmed/30092266

» Association of inadequately controlled disease and disease severity with patient-reported disease burden in adults with atopic dermatitis.

Simpson EL, et al. JAMA Dermatol. 2018;154(8):903-912.

https://jamanetwork.com/journals/jamadermatology/fullarticle/2686155

» 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

» Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape.

Boguniewicz M, et al. Ann Allergy Asthma Immunol. 2018;120(1):10-22. https://www.annallergy.org/article/S1081-1206(17)31260-7/pdf

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RESOURCE CENTER

Management of Atopic Dermatitis

» Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement.

Drucker AM, et al. Br J Dermatol. 2018;178(3):768-775. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901393/

» Application of moisturizer to neonates prevents development of atopic dermatitis.

Horimukai K, et al. J Allergy Clin Immunol. 2014;134(4):824-830. https://www.ncbi.nlm.nih.gov/pubmed/25282564

» New and emerging therapies for pediatric atopic dermatitis.

Nguyen HL, et al. Pediatric Drugs. 2019;21(4):239-260

https://link.springer.com/article/10.1007%2Fs40272-019-00342-w

» Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus.

Silverberg JI. J Allergy Clin Immunol. 2019 Aug 23 pii: S00916749(19)31099-1. [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pubmed/31449914

» Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE).

Simpson EL, et al. J Am Acad Dermatol. 2018;78(5):863-871. https://www.jaad.org/article/S0190-9622(18)30102-6/fulltext

» When does atopic dermatitis warrant systemic therapy?

Recommendations from an expert panel of the International Eczema Council.

RESOURCE CENTER

Simpson EL, et al. J Am Acad Dermatol. 2017;77(4):623-633. https://www.jaad.org/article/S0190-9622(17)31944-8/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. https://www.ncbi.nlm.nih.gov/pubmed/27690741

» Treatment of atopic dermatitis with tralokinumab, an antiIL-13 mAb. Wollenberg A, et al. J Allergy Clin Immunol. 2019;143(1):135-141. https://www.jacionline.org/article/S0091-6749(18)30850-9/fulltext

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