Clinical Issues in Psoriasis

This activity is jointly provided by Clinical and Patient Educators Association (CPEA) and Integritas Communications.

This activity is supported by an independent educational grant from Boehringer Ingelheim.

This program is independent and is not part of the official AAD Annual Meeting, as planned by its Scientific Assembly Committee. This program does not qualify for continuing medical education (CME) credit.

MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

Jeffrey J. Crowley, MD, FAAD Bakersfield Dermatology and Skin Cancer Medical Group Bakersfield, California

Dr. Jeffrey Crowley earned his bachelor’s and master’s of science from Stanford University in biological science. Continuing at Stanford, he received his medical degree and completed his internship and residency in the Department of Dermatology at Stanford University Affiliated Hospitals. He served as Chief Resident and is board certified through the American Board of Dermatology as well as being a Fellow of the American Academy of Dermatology.

Dr. Crowley has served as clinical faculty for both the University of California, Los Angeles, and Stanford University Departments of Dermatology. He has been principal investigator for more than 50 phase 2 and 3 clinical trials for psoriasis, atopic dermatitis, and hidradenitis suppurativa. He has over 50 peer-reviewed publications including articles in the New England Journal of Medicine. In 2016, he graduated with commendation from the Harvard Global Scholars Clinical Research Training Program, a 1-year postdoctoral fellowship focusing on clinical research. Dr. Crowley practices at Bakersfield Dermatology and Skin Cancer Medical Group in California and serves on the Medical Board of the National Psoriasis Foundation.

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Neil J. Korman, MD, PhD FACULTY

Professor of Dermatology Department of Dermatology Case Western Reserve University Director, Clinical Trials Unit Clinical Director Murdough Family Center for Psoriasis University Hospitals Cleveland Medical Center Cleveland, Ohio Dr. Neil Korman earned his medical degree at Case Western Reserve University School of Medicine where he also earned his PhD in Biomedical Engineering. He proceeded with his Dermatology Residency at Case Western Reserve University and University Hospitals Cleveland Medical Center followed by an immunodermatology research fellowship at the National Cancer Institute, Dermatology Branch, prior to joining Case Western Reserve University and University Hospitals Cleveland Medical Center in 1990.

Dr. Korman is a Professor of Dermatology, Director of the Clinical Trials Unit, Clinical Director of the Murdough Family Center for Psoriasis, and Director of the Skin Immunopathology Laboratory at Case Western Reserve University and University Hospitals Cleveland Medical Center Department of Dermatology. His special interests are psoriasis, immunobullous diseases, and atopic dermatitis. As Director of the Clinical Trials Unit, he has been involved in multiple clinical trials for patients with autoimmune blistering diseases, atopic dermatitis, cutaneous T cell lymphoma, cutaneous lupus erythematosus, actinic keratosis, alopecia areata, lichen planus, pyoderma gangrenosum, prurigo nodularis, tinea pedis, tinea capitis, and onychomycosis. Dr. Korman has more than 15 years of experience in more than 75 phase 1-4 psoriasis clinical trials including trials of all of the major biologic agents that have been approved for psoriasis as well as several translational, mechanism of action studies in patients with psoriasis.

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Abby S. Van Voorhees, MD FACULTY

Chair and Residency Director Department of Dermatology Eastern Virginia Medical School Norfolk, Virginia

Dr. Abby Van Voorhees is a professor, chair, and residency director of the department of dermatology at the Eastern Virginia Medical School. She obtained her bachelor’s degree from Brown University in 1979 in biology and received her medical degree from Yale University in 1983. She completed her dermatology residency at the Yale-New Haven Hospital in 1988, serving as the chief resident from July 1987 to 1988. Prior to her current position, she was the Director of Psoriasis Services and Phototherapy Units at the University of Pennsylvania after her work at the University of Connecticut Department of Medicine.

Dr. Van Voorhees is the chair of the Medical Board of the National Psoriasis Foundation and is also on the Board of Directors of the American Academy of Dermatology. She previously held the position of Medical Editor of Dermatology World. Additionally, she has served on several of the American Academy of Dermatology’s committees and task forces, including serving as the chair for the Guidelines of Care task force. The author of over 90 publications, Dr. Van Voorhees has been active in clinical research issues in dermatology, particularly those related to the treatment of psoriasis.

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TARGET AUDIENCE

The educational design of this activity addresses the needs of dermatologists, clinical immunologists, and other clinicians involved in the treatment and management of patients with pustular psoriasis.

EDUCATIONAL OBJECTIVES PREAMBLE

After completing this activity, the participant should be better able to: • Describe the genetic and pathophysiologic mechanisms that contribute to the development of pustular psoriasis, including factors that have informed the development of new therapies • Comprehensively assess patients with suspected pustular psoriasis based on clinical manifestations, diagnostic criteria, and disease severity • Describe the mechanistic rationales and clinical evidence for current and emerging biologic therapies for the treatment of generalized pustular psoriasis and palmoplantar pustulosis • Individualize therapeutic regimens for pustular psoriasis, with a focus on generalized disease subtypes and palmoplantar pustulosis

PROGRAM OVERVIEW

Pustular psoriasis is a relatively rare form of psoriasis and has historically been classified into generalized and localized forms of the disease.1 Generalized pustular psoriasis is characterized by widespread sterile pustules on erythematous skin, recurrent fever, and systemic flushing and malaise.1,2 Palmoplantar pustulosis, a localized form, is characterized by erythema, pruritis, burning, and pain on the palms of the hands and soles of the feet. Recent evidence suggests that IL36RN mutations are the most common genetic aberration linked to pustular psoriasis, with the allelic frequency distinguishing generalized pustular psoriasis and palmoplantar pustulosis; the former shows a 4 to 1 increase versus the latter.3 Whether pustular psoriasis presents as localized or generalized, patients are subject to significant health risks and poor quality of life outcomes due to both skin and systemic manifestations. Patients may be subject to delays in diagnosis, in part because the disease states are relatively rare and there 6

REFERENCES 1.

Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(2):279-288.

2. Fujita H, Terui T, Hayama K, et al. Japanese guidelines for the management and treatment of generalized pustular psoriasis: the new pathogenesis and treatment of GPP. J Dermatol.

2018;45(11):1235-1270.

3. Twelves S, Mostafa A, Dand N, et al. Clinical and genetic differences between pustular psoriasis subtypes. J Allergy Clin Immunol. 2018. [Epub ahead of print.]

4. Benjegerdes KE, Hyde K, Kivelevitch D, Mansouri B. Pustular psoriasis: pathophysiology and current treatment perspectives. Psoriasis (Auckl). 2016;6:131-144.

5. Bachelez H, Choon S, Marrakchi S, et al. Efficacy and safety of BI 655130, an antiinterleukin-36 receptor antibody, in patients with acute generalized pustular psoriasis.

EADV Congress; September 12-16, 2018; Paris, France. Abstract D3T01.1E.

PROGRAM AGENDA

7:00 pm –7:10 pm Preactivity Questionnaire and Faculty Introductions 7:10 pm –7:30 pm Introduction to Pustular Psoriasis Pathophysiology 7:30 pm –7:50 pm Evaluating Patients With Generalized Pustular Psoriasis or Palmoplantar Pustulosis 7:50 pm –8:20 pm Evolving Therapeutic Approaches for Patients With Pustular Psoriasis 8:20 pm –8:40 pm

Practical Application: Patient Case Discussion

8:40 pm –9:00 pm

Postactivity Questionnaire and Q&A Session

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PREAMBLE

are little solid epidemiologic data.4 Dermatologists are faced with limited guidance on selecting therapies for patients with any of the pustular psoriasis subtypes.1 Biologic agents for pustular psoriasis and palmoplantar pustulosis are being examined in clinical trials.

These include some biologics approved for psoriasis as well as agents with novel therapeutic targets, such as an anti-interleukin (IL)-36 receptor antibody.5 This Clinical Issues symposium will use both lecture and faculty discussion among leading dermatology experts to explore many of these issues, with an emphasis on evolving diagnostic and management strategies for generalized pustular psoriasis and palmoplantar pustulosis.

FEE INFORMATION

There is no fee for this educational activity.

PREAMBLE

DISCLOSURE OF CONFLICTS OF INTEREST

Clinical and Patient Educators Association (CPEA) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity.

All identified conflicts of interest are thoroughly vetted by CPEA for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

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: Jeffrey J. Crowley, MD, FAAD Consultant/Independent Contractor: AbbVie Inc., Eli Lilly and Company, Janssen Therapeutics, Novartis Pharmaceuticals Corporation; Grant/ Research Support: AbbVie Inc., Eli Lilly and Company, Janssen Therapeutics, Merck & Co., Inc., MC2 Therapeutics A/S, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc., Verrica Pharmaceuticals Inc., UCB, Inc.; Speakers Bureau: AbbVie Inc., Eli Lilly and Company, Janssen Therapeutics, Sun Pharmaceutical Industries, Inc., UCB, Inc. Neil J. Korman, MD, PhD Consultant/Independent Contractor: Novartis Pharmaceuticals Corporation; Grant/Research Support: AbbVie Inc., Celgene Corporation, Dermira, Inc., Eli Lilly and Company, Menlo Therapeutics Inc., Merck & Co., Inc., Pfizer Inc., Syntimmune, Inc.; Honoraria/Advisory Board: AbbVie Inc., Celgene Corporation, Eli Lilly and Company, Janssen Therapeutics, Novartis Pharmaceuticals Corporation; Speakers Bureau: AbbVie Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc.

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Abby S. Van Voorhees, MD Consultant/Independent Contractor: Celgene Corporation, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, UCB, Inc.; Grant/Research Support: Celgene Corporation, Eli Lilly and Company; Honoraria: DermTech, Inc., WebMD

PREAMBLE

The planners and managers 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: Andrea Funk Nothing to disclose Gena Dolson Nothing to disclose Jim Kappler, PhD Nothing to disclose

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. Clinical and Patient Educators Association (CPEA) and Integritas Communications do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

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 in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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CLINICAL PRACTICE GUIDELINES »»Japanese guidelines for the management and treatment of generalized pustular psoriasis: the new pathogenesis and treatment of GPP. Fujita H, et al. J Dermatol. 2018;45(11):1235-1270. https://onlinelibrary.wiley.com/doi/abs/10.1111/13468138.14523

»»Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation.

Robinson A, et al. J Am Acad Dermatol. 2012;67(2):279-288. https://www.jaad.org/article/S0190-9622(11)00304-5/ fulltext

PATIENT RESOURCES »»National Psoriasis Foundation

The NPF website provides an overview of symptoms, triggers, types, and treatment. https://www.psoriasis.org/about-psoriasis/types/pustular

»»Psoriasis and Psoriatic Arthritis Alliance

RESOURCE CENTER

The PAPAA provides an overview of pustular psoriasis and its various forms as well as available treatment options. http://www.papaa.org/further-information/ pustular-psoriasis

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SUGGESTED READING »»Pustular psoriasis: pathophysiology and current treatment perspectives.

Benjegerdes KE, et al. Psoriasis (Auckl). 2016;6:131-144. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683122/

»»Increased expression of IL-17A and limited involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised controlled trial.

Bissonnette R, et al. J Eur Acad Dermatol Venereol. 2014;28(10):1298-1305. https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.12272

»»Generalized pustular psoriasis—a model disease for specific targeted immunotherapy, systematic review.

Boehner A, et al. Exp Dermatol. 2018;27(10):1067-1077. https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13699

»»Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia.

Choon SE, et al. Int J Dermatol. 2014;53(6):676-684. https://onlinelibrary.wiley.com/doi/abs/10.1111/ijd.12070

»»Novel findings of Langerhans cells and interleukin-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis.

Hagforsen E, et al. Br J Dermatol. 2010;163(3):572-579. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2133.2010.09819.x

RESOURCE CENTER

»»Generalized pustular psoriasis: a review and update on treatment.

Hoegler KM, et al. J Eur Acad Dermatol Venereol. 2018;32(10):1645-1651. https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.14949

»»Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis.

Marrakchi S, et al. N Engl J Med. 2011;365(7):620-628. https://www.nejm.org/doi/10.1056/NEJMoa1013068

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»»What do we know about palmoplantar pustulosis?

Misiak-Galazka M, et al. J Eur Acad Dermatol Venereol. 2017;31(1):38-44. https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.13846

»»Patients with palmoplantar pustulosis have increased IL-17 and IL-22 levels both in the lesion and serum.

Murakami M, et al. Exp Dermatol. 2011;20(10):845-847. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-0625.2011.01325.x

»»Palmoplantar psoriasis and palmoplantar pustulosis: current treatment and future prospects.

Raposo I, Torres T. Am J Clin Dermatol. 2016;17(4):349-358. https://link.springer.com/article/10.1007%2Fs40257-016-0191-7

»»Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: results from a 52-week, open-label, phase 3 study (UNCOVER-J).

Saeki H, et al. J Dermatol. 2017;44(4):355-362. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412888/

»»The efficacy of biologic therapy for the management of palmoplantar psoriasis and palmoplantar pustulosis: a systematic review.

Sanchez IM, et al. Dermatol Ther (Heidelb). 2017;7(4):425-446. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698206/

»»Guselkumab, a human interleukin-23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: efficacy and safety analyses of a 52-week, phase 3, multicenter, open-label study.

RESOURCE CENTER

Sano S, et al. J Dermatol. 2018;45(5):529-539. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947137/

»»The genetic background of generalized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants.

Sugiura K. J Dermatol Sci. 2014;74(3):187-192. https://www.jdsjournal.com/article/S0923-1811(14)00054-1/fulltext

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»»Efficacy and safety of guselkumab, an anti-interleukin 23 monoclonal antibody, for palmoplantar pustulosis: a randomized clinical trial.

Terui T, et al. JAMA Dermatol. 2018;154(3):309-316. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885837/

»»Clinical and genetic differences between pustular psoriasis subtypes.

Twelves S, et al. J Allergy Clin Immunol. 2018. [Epub ahead of print]. https://www.jacionline.org/article/S0091-6749(18)31039-X/fulltext

»»Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study.

RESOURCE CENTER

Yamasaki K, et al. Br J Dermatol. 2017;176(3):741-751. https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.14702

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