A CME/CE CERTIFIED SUPPLEMENT TO

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Skin Disease Education Foundation’s 11th Annual Psoriasis Forum Introduction Identifying and Managing Complications and Comorbidities in Patients With Psoriasis Update on New and Emerging Therapies in the Management of Psoriasis TNF Inhibitors in Psoriasis: A Review Screening and Monitoring Before and During Systemic Therapy: Recommendations for Patients With Psoriasis Post-Test and Evaluation Form

Original Release Date: April 2015 Most Recent Review Date: April 2015 Expiration Date: April 30, 2016 Estimated Time to Complete Activity: 2.0 hours Jointly provided by

Faculty Francisco A. Kerdel, BSc, MBBS, Chair Director of Inpatient Dermatology University of Miami Hospital Professor of Dermatology and Vice Chairman Florida International University Miami, Florida

Kristina Callis Duffin, MD, MS Assistant Professor, Dermatology University of Utah Salt Lake City, Utah

Kenneth B. Gordon, MD Professor of Dermatology Northwestern University Feinberg School of Medicine Chicago, Illinois

Craig L. Leonardi, MD Clinical Professor of Dermatology Saint Louis University Central Dermatology St Louis, Missouri

Supported by educational grants from

AbbVie Inc., Amgen Inc., Celgene Corporation, and Novartis Pharmaceuticals Corporation

Highlights of Skin Disease Education Foundation’s 11th Annual Psoriasis Forum

A CME/CE CERTIFIED SUPPLEMENT TO

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4 Introduction 5 Identifying and Managing Complications and Comorbidities in Patients With Psoriasis Kristina Callis Duffin, MD, MS, and Craig L. Leonardi, MD



9 Update on New and Emerging Therapies in the Management of Psoriasis Kenneth B. Gordon, MD, and Craig L. Leonardi, MD

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TNF Inhibitors in Psoriasis: A Review

Francisco A. Kerdel, BSc, MBBS Reprinted from Seminars in Cutaneous Medicine and Surgery The manuscript was originally published as a supplement to Seminars in Cutaneous Medicine and Surgery, Vol. 34, No. 2S, March 2015. It has been reviewed and approved by the faculty as well as the Editors of Seminars in Cutaneous Medicine and Surgery.

The Faculty acknowledge the editorial assistance of Global Academy for Medical Education, LLC, and Joanne Still, medical writer, in the development of this supplement. This continuing medical education (CME) supplement was developed from selected presentations at the Skin Disease Education Foundation 11th Annual Psoriasis Forum held on October 31, 2014. Neither the editors of Dermatology News nor the Editorial Advisory Board nor the reporting staff contributed to its content. The opinions expressed are those of the faculty and do not necessarily reflect the views of the supporter or of the Publisher.

Copyright © 2015 by Global Academy for Medical Education, LLC, Frontline Medical Communications Inc. and its Licensors. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of the Publisher. Global Academy for Medical Education, LLC, will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

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15 Screening and Monitoring Before and During Systemic Therapy: Recommendations for Patients With Psoriasis Kristina Callis Duffin, MD, MS

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Post-Test 19 Evaluation Form

Faculty Francisco A. Kerdel, BSc, MBBS, Chair Director of Inpatient Dermatology University of Miami Hospital Professor of Dermatology and Vice Chairman Florida International University Miami, Florida Kristina Callis Duffin, MD, MS Assistant Professor, Dermatology University of Utah Salt Lake City, Utah

Kenneth B. Gordon, MD Professor of Dermatology Northwestern University Feinberg School of Medicine Chicago, Illinois

Craig L. Leonardi, MD

Clinical Professor of Dermatology Saint Louis University Central Dermatology St Louis, Missouri

Skin Disease Education Foundation 11th Annual Psoriasis Forum • globalacademycme.com

Highlights of Skin Disease Education Foundation’s 11th Annual Psoriasis Forum Release Date: April 2015 Expiration Date: April 30, 2016 Estimated Time to Complete Activity: 2.0 hours To get instant CME/CE credits online, go to http://Tinyurl.com/SDEF11Psoriasis. Upon successful completion of the online test and evaluation form, you will be directed to a Web page that will allow you to receive your certificate of credit via e-mail or you may print it at that time. If you have any questions or difficulties with this activity, please contact the Global Academy for Medical Education office at [email protected].

Accreditation Statements

Physicians: This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Rutgers, The State University of New Jersey and Global Academy for Medical Education. Rutgers, The State University of New Jersey is accredited by the ACCME to provide continuing medical education for physicians.  Rutgers, The State University of New Jersey designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.  Nurses: Rutgers, The State University of New Jersey, Center for Continuing and Outreach Education (CCOE) is an approved provider of continuing nursing education by the New Jersey State Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. Provider Number P173-12/12-15. This activity is awarded 1.94 contact hours. (60 minute CH) Nurses should only claim those contact hours actually spent participating in the activity.

Target Audience

This educational activity is intended for dermatologists, family physicians, physician assistants, nurses, nurse practitioners, and other clinicians who treat patients with psoriasis.

Educational Needs

The estimated 7 million Americans with psoriasis and their clinicians can now choose from an expanded—and soon to be even longer—list of effective and safe medications to treat their disease.This is especially true of systemic therapies used to treat patients with moderate to severe disease. The approval of several tumor necrosis factor (TNF) inhibitors for psoriasis was followed by the availability of biologic agents and small molecules that target other pathogenetic pathways. Additional agents having a variety of mechanisms of action currently are being investigated in phase III clinical trials. To ensure the optimum management of each patient, clinicians must remain up-to-date on ongoing research involving both currently available and emerging treatments. Clinicians will benefit from this educational activity, which provides an update regarding the effective and safe use of the systemic agents now available as well as the emerging therapies that show promise. The articles in this supplement focus on appropriate patient selection for various therapies, laboratory and other screening modalities prior to institution of treatment to identify infectious diseases and other comorbidities, recommendations for monitoring patients during treatment, and emerging therapies that may become available in the near future.

Learning Objectives

By reading and studying this supplement, participants should be better able to: • Discuss the roles of topical and systemic therapies, including biologic and small molecule agents, in the treatment of moderate to severe psoriasis. • Assess patients for comorbidities and manage psoriasis as well as associated comorbidities. • Describe the mechanisms of action, efficacy, and safety of currently available and newly emerging biologic and small molecule agents used to treat psoriasis. • Review their current practice protocols for screening and monitoring patients with psoriasis who are candidates for or are being treated with biologic and small molecule agents and update these as needed according to evidencebased recommendations. • Incorporate updated monitoring strategies for the safe use of methotrexate and cyclosporine, as monotherapy or when combined with biologic agents. • Evaluate the results of clinical studies on new and emerging treatments for psoriasis.

Disclosure Declarations Individuals in a position to control the content of this educational activity are required to disclose: 1) the existence of any relevant financial relationship with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients with the exemption of non-profit or government organizations and non-health care related companies, within the past 12 months; and 2) the identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.

Faculty

Kristina Callis Duffin, MD, MS, Grant/Research: AbbVie Inc., Amgen Inc., Bristol-Myers Squibb Company, Celgene Corporation, Eli Lilly and Company, Janssen Biotech, Inc., Pfizer Inc., and Stiefel Laboratories, Inc. Consultant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis Pharmaceuticals Corporation, Pfizer, and XenoPort, Inc. Scientific Advisory Board: Eli Lilly and Janssen. Kenneth B. Gordon, MD, Grant/Research: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, and Merck & Co., Inc. Consultant: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, and Pfizer. Francisco A. Kerdel, BSc, MBBS, Grant/Research: AbbVie, Amgen, AstraZeneca, Celgene, Galderma Laboratories, L.P., Janssen, Novartis, Pfizer, and Valeant. Advisory Board: Celgene. Speakers Bureau: AbbVie, Amgen, Celgene, Galderma, and Janssen. Craig L. Leonardi, MD, Grant/Research: AbbVie, Amgen, Celgene, Coherus BioSciences, Dermira Inc., Eli Lilly, Galderma Laboratories, L.P., Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sandoz Inc., Stiefel, and Wyeth. Consultant: AbbVie, Amgen, Dermira, Eli Lilly, Janssen, LEO, Pfizer, Sandoz, and UCB, Inc. Speakers Bureau: AbbVie and Celgene. In order to help ensure content objectivity, independence, and fair balance, and to ensure that the content is aligned with the interest of the public, CCOE has resolved all potential and real conflicts of interest through content review by a non-conflicted, qualified reviewer. This activity was peer-reviewed for relevance, accuracy of content, and balance of presentation by: Geraldine Bocchieri, RN, BSN, Nurse, Department of Dermatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. Ms. Bocchieri has no relevant financial relationships to disclose. Field Testers: This activity was pilot-tested for time required by: Physicians: Lilia Correa, MD, and Omar Noor, MD. Nurses: Janel Bowman, RN; Claudia Carron, MSN, RN, NE-BC; and Carol Ruland, RN. The field testers have no relevant financial relationships to disclose. Rutgers, The State University of New Jersey: Tristan Nelsen, MNM, CMP, and Elizabeth Ward, MSJ, have no relevant financial relationships to disclose. Global Academy for Medical Education Staff: Shirley V. Jones, MBA; Sylvia H. Reitman, MBA, DipEd; and Joanne Still, BA, have no relevant financial relationships to disclose.

Off-Label/Investigational Use Disclosure This activity discusses the following investigational products, not yet approved: brodalumab, guselkumab, ixekizumab, and tildrakizumab. Also discussed is the investigational use in clinical trials of patients with psoriasis of the approved agent, tofacitinib. This continuing education supplement was developed from Skin Disease Education Foundation’s 11th Annual Psoriasis Forum, held October 31, 2014, in Las Vegas, NV. The Guest Editors acknowledge the editorial assistance of Global Academy for Medical Education and Joanne Still, medical writer, in the development of this supplement. The manuscript was reviewed and approved by the Guest Editors as well as the Editors of Seminars in Cutaneous Medicine and Surgery. The ideas and opinions expressed in this supplement are those of the Guest Editors and do not necessarily reflect the views of the supporters, Global Academy for Medical Education, Rutgers, or of the Publisher.

Jointly provided by

Supported by educational grants from

AbbVie Inc., Amgen Inc., Celgene Corporation, and Novartis Pharmaceuticals Corporation Skin Disease Education Foundation 11th Annual Psoriasis Forum • globalacademycme.com 

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Introduction

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linicians who treat patients with psoriasis today practice in times that are both more challenging and potentially more rewarding than ever. Both are presented by a rapidly evolving body of knowledge and literature regarding the pathophysiology and, therefore, the treatment of psoriasis. This continuing medical education activity is derived from selected presentations offered at the Skin Disease Education Foundation (SDEF) 11th Annual Psoriasis Forum. The articles chosen for inclusion in this supplement provide highlights of the presentations that were deemed most relevant and practically helpful to our colleagues in clinical practice. In the first article, the authors discuss some of the most important disease states that commonly exist with psoriasis as comorbid conditions, including those that may increase morbidity and mortality and adversely affect quality of life. They also address the multiple comorbidities that increase the risk for cardiovascular disease in patients with psoriasis, and the use of biologic therapy in patients with psoriasis who have comorbid conditions or complications. Following the introduction of tumor necrosis factor (TNF) inhibitors, further advances in the understanding of psoriasis pathophysiology led to the development of yet more choices for the effective and safe treatment of patients who are candidates for systemic therapy. These newer and emerging treatments, discussed in the second article, include the interleukin (IL)-12/23 blocker ustekinumab (approved in 2009); the IL-17 inhibitors secukinumab (approved in January 2015) and ixekizumab; the IL-17 receptor blocker brodalumab; the IL-23 blockers tildrakizumab and guselkumab; and the small molecules apremilast (approved in 2014) and tofacitinib. The TNF inhibitors were the first biologic agents to be approved by the US Food and Drug Administration for the treatment of psoriasis and remain a cornerstone of treatment for patients with moderate to severe disease. The third article in this supplement reviews the mechanisms of action and efficacy and safety data on adalimumab, etanercept, and infliximab (the 3 TNF inhibitors approved for psoriasis), and summarizes some observations from both clinical and research experience that may help clinicians maximize the efficacy of these agents. The fourth article provides a practical approach to screening patients prior to initiation of treatment with biologic agents and other systemic treatments as well as monitoring patients during therapy. The goal of such surveillance is to individualize treatment outcomes for optimum efficacy and minimum adverse events. In addition to the articles in this supplement, readers are invited to access selected presentations from the 2014 forum. These are available online at http://tinyurl.com/SDEF11Psoriasis. We hope our colleagues find this supplement and the presentations helpful.

Francisco A. Kerdel, BSc, MBBS

Director of Inpatient Dermatology University of Miami Hospital Professor of Dermatology and Vice Chairman Florida International University Miami, Florida

Journal Supplement Chair

Publication of this CME/CE article was jointly provided by Rutgers, The State University of New Jersey and Global Academy for Medical Education, LLC, with Skin Disease Education Foundation (SDEF) and is supported by educational grants from AbbVie Inc., Amgen Inc., Celgene Corporation, and Novartis Pharmaceuticals Corporation. Dr Kerdel has received an honorarium for his participation in this activity. He acknowledges the editorial assistance of Joanne Still, medical writer, and Global Academy for Medical Education in the development of this continuing medical education journal article. Francisco A. Kerdel, BSc, MBBS, Grant/Research: AbbVie, Amgen, AstraZeneca, Celgene, Galderma Laboratories, L.P., Janssen, Novartis, Pfizer, and Valeant. Advisory Board: Celgene. Speakers Bureau: AbbVie, Amgen, Celgene, Galderma, and Janssen. Address reprint requests to: Francisco A. Kerdel, BSc, MBBS, Florida Academic Dermatology Centers, 1400 NW 12 Avenue, Suite 4, Miami, FL 33136; [email protected]

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Skin Disease Education Foundation 11th Annual Psoriasis Forum • globalacademycme.com

Identifying and Managing Complications and Comorbidities in Patients With Psoriasis Kristina Callis Duffin, MD, MS,* and Craig L. Leonardi, MD†

Abstract The common comorbidities of cutaneous psoriasis include psoriatic arthritis (PsA), Crohn’s disease, uveitis, and depression. In addition, cardiovascular disease risk factors (including metabolic syndrome) are seen more frequently among patients with psoriasis, and strong epidemiologic evidence has demonstrated that psoriasis is independently associated with myocardial infarction. Because these comorbid conditions and other medical complications adversely affect morbidity and mortality in patients with psoriasis, dermatologists can play an important role in promptly identifying and, when necessary, referring patients for further workup and treatment when signs or symptoms of these comorbidities or complications are observed. Semin Cutan Med Surg 34(supp2):S30-S33 © 2015 published by Frontline Medical Communications

Keywords Biologic agents; cardiovascular disease risk factors; chronic kidney disease; immune-mediated inflammatory diseases; psoriasis; psoriatic arthritis; viral hepatitis

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soriasis is a multifaceted disease that is associated with multiple disease states—including psoriatic arthritis (PsA), Crohn’s disease, uveitis, and depression—and behaviors (specifically, excess alcohol use and cigarette smoking). All of these have the potential to increase morbidity and mortality and to adversely affect quality of life for patients with psoriasis. In addition, psoriasis is associated with multiple comorbidities that increase the risk for cardiovascular disease (CVD), including obesity, dyslipidemia (hypertriglyceridemia and low high-density lipoprotein [HDL] level), hypertension, and elevated fasting serum

* Assistant Professor, Dermatology, University of Utah, Salt Lake City, Utah. † Clinical Professor of Dermatology, Saint Louis University, Central Dermatology, St Louis, Missouri. Publication of this CME/CE article was jointly provided by Rutgers, The State University of New Jersey and Global Academy for Medical Education, LLC, with Skin Disease Education Foundation (SDEF) and is supported by educational grants from AbbVie Inc., Amgen Inc., Celgene Corporation, and Novartis Pharmaceuticals Corporation. Dr Duffin and Dr Leonardi have received an honorarium for their participation in this activity. They acknowledge the editorial assistance of Joanne Still, medical writer, and Global Academy for Medical Education in the development of this continuing medical education journal article. Kristina Callis Duffin, MD, MS, Grant/Research: AbbVie, Amgen, Bristol-Myers Squibb Company, Celgene, Eli Lilly and Company, Janssen Biotech, Inc., Pfizer Inc., and Stiefel Laboratories, Inc. Consultant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and XenoPort, Inc. Scientific Advisory Board: Eli Lilly and Janssen. Craig L. Leonardi, MD, Grant/Research: AbbVie, Amgen, Celgene, Coherus BioSciences, Dermira Inc., Eli Lilly, Galderma Laboratories, L.P., Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sandoz Inc., Stiefel, and Wyeth. Consultant: AbbVie, Amgen, Dermira, Eli Lilly, Janssen, LEO, Pfizer, Sandoz, and UCB, Inc. Speakers Bureau: AbbVie and Celgene. Address reprint requests to: Craig L. Leonardi, MD, Central Dermatology, 1034 S. Brentwood Boulevard, St Louis, MO 63117; [email protected].

glucose level. Moreover, psoriasis is independently associated with myocardial infarction (MI). Although dermatologists may not treat these conditions per se, awareness of psoriasis comorbidities and complications is crucial so that patients can be promptly identified and referred, when necessary, to colleagues in the appropriate specialties. This article focuses on identifying and managing complications and comorbidities in patients with psoriasis and offers practical observations about biologic therapy in this patient population.

Psoriasis and CVD Risk Factors and MI Severe psoriasis is associated with an increased prevalence of metabolic syndrome, defined as the presence of 3 or more of the following: increased waist circumference (abdominal obesity), hypertension, hypertriglyceridemia, reduced HDL, and insulin resistance/increased serum glucose. Metabolic syndrome is recognized as a chronic inflammatory state and is associated with marked increases in cardiovascular mortality; an estimated 25% of individuals in the United States today have metabolic syndrome.1 In a landmark study, Sommer and colleagues2 demonstrated an increased prevalence of metabolic syndrome in patients with moderate to severe psoriasis. In this study, investigators at the University of Kiel, Germany, compared the charts of 580 patients who were hospitalized for plaque psoriasis with the records of more than 1,000 patients who were admitted for localized melanoma surgery during the same time period. The charts, screened for the presence of concomitant internal diseases, showed that the patients with psoriasis also had significantly greater prevalence of diabetes (P