Milestones in Drug Therapy MDT Series Editors Prof. Dr. Michael J. Parnham PhD Prof. Dr. J. Bruinvels Director of Preclinical Discovery Sweelincklaan 75 Centre of Excellence in Macrolide Drug Discovery NL-3723 JC Bilthoven GlaxoSmithKline Research Centre Zagreb Ltd. The Netherlands Prilaz baruna Filipovića 29 HR-10000 Zagreb Croatia Treatment of Psoriasis Edited by Jeffrey M. Weinberg Birkhäuser Basel . Boston . Berlin Editor Jeffrey M. Weinberg Department of Dermatology St. Luke’s-Roosevelt Hospital Center 1090 Amsterdam Avenue, Suite 11 D New York, NY 10025 USA Advisory Board J.C. Buckingham (Imperial College School of Medicine, London, UK) R.J. Flower (The William Harvey Research Institute, London, UK) P. Skolnick (DOV Pharmaceuticals Inc., Hackensack, NJ, USA) Library of Congress Control Number: 2007936202 Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the internet at http://dnb.ddb.de ISBN: 978-3-7643-7722-9 Birkhäuser Verlag AG, Basel – Boston – Berlin The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names, trademarks etc. in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use. This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. For any kind of use, permission of the copyright owner must be obtained. © 2008 Birkhäuser Verlag AG, P.O. Box 133, CH-4010 Basel, Switzerland Part of Springer Science+Business Media Printed on acid-free paper produced from chlorine-free pulp. TFC ∞ Cover illustration: With the friendly permission by the American Society for Clinical Investigation Printed in Germany ISBN 978-3-7643-7722-9 e-ISBN 978-3-7643-7724-3 9 8 7 6 5 4 3 2 1 www. birkhauser.ch V Contents List of contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VII Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX Alissa Cowden and Abby S. Van Voorhees Introduction:History of psoriasis and psoriasis therapy . . . . . . . . . . . . 1 Marissa D. Newman and Jeffrey M. Weinberg The pathophysiology of psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Allison J. Brown and Neil J. Korman Psoriasis and psoriatic arthritis:a clinical review . . . . . . . . . . . . . . . . . 23 Paru R. Chaudhari,Dana K. Stern and Mark G. Lebwohl Topical therapy I:corticosteroids and vitamin D analogs . . . . . . . . . . . 41 Paru R. Chaudhari,Dana K. Stern and Mark G. Lebwohl Topical therapy II:retinoids,immunomodulators,and others . . . . . . . . 57 Rahat S. Azfar and Abby S. Van Voorhees Ultraviolet and laser therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 EdwardM. Prodanovic and Neil J.Korman Traditional systemic therapy I:methotrexate and cyclosporine . . . . . . 103 Sejal K. Shah and JeffreyM. Weinberg Traditional systemic therapy II:retinoids and others (hydroxyurea, thiopurine antimetabolites,mycophenlic acid,sulfasalazine) . . . . . . . . 121 Jeffrey M. Weinberg Biologic therapy for psoriasis:an overview of infliximab, etanercept,adalimumab,efalizumab,and alefacept . . . . . . . . . . . . . . . 141 Maria R. Robinson and Neil J.Korman Biologic and oral therapies in development for the treatment of psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Amanda B. Sergay,Matthew Silvan and Jeffrey M. Weinberg Quality of life issues in psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 VII List of contributors Rahat S. Azfar,Department of Dermatology,University of Pennsylvania,3600 Spruce St,2 Maloney,Philadelphia,PA 19104,USA Allison J. Brown, Department of Dermatology, Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland,OH 44106,USA Paru R. Chaudhari, Mount Sinai School of Medicine, Department of Dermatology, 5 E 98th St 5th Floor, New York, NY 10029, USA; e-mail: [email protected] Alissa Cowden,University of Pennsylvania,Philadelphia,PA 19104,USA Neil J. Korman, Department of Dermatology, Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland,OH 44106,USA; e-mail:[email protected] Mark G. Lebwohl, Mount Sinai School of Medicine, Department of Dermatology, 5 E 98th St 5th Floor, New York, NY 10029, USA; e-mail: [email protected] Marissa D. Newman, UMDNJ-Robert Wood Johnson Medical School New Jersey,New Jersey,08902,USA; e-mail:[email protected] Edward M. Prodanovic, Department of Dermatology, Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, 11100 Euclid Ave,Cleveland,OH 44106,USA Maria R. Robinson,Department of Dermatology,Murdough Family Center for Psoriasis,University Hospitals Case Medical Center,Cleveland,OH 44106, USA Sejal K. Shah, St. Luke’s-Roosevelt Hospital Center, Department of Dermatology, 1090 Amsterdam Avenue, Suite 11D, New York, NY 10025, USA; e-mail:[email protected] Amanda B. Sergay, Department of Dermatology, St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, New York, NY, USA; e-mail:[email protected] Matthew Silvan, Department of Dermatology, St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center,New York,NY,USA Dana K. Stern,Mount Sinai School of Medicine,Department of Dermatology, 5E98th St 5th Floor,NewYork,NY 10029,USA Abby S. Van Voorhees, Psoriasis and Phototherapy Treatment Center, 2M44 Rhoads Pavilion,3600 Spruce Street,Philadelphia,PA 19104,USA; e-mail: [email protected] Jeffrey M. Weinberg, Department of Dermatology, St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center,1090 Amsterdam Avenue, Suite 11D,NewYork,NY 10025,USA; e-mail:[email protected] IX Preface Psoriasis is an inherited skin disease that has been diagnosed in 4.5 million adults in the US. About 10–30% of people with psoriasis also develop psori- atic arthritis, which causes pain, stiffness and swelling in and around the joints. The past 25 years of research and clinical practice have revolutionized our understanding of the pathogenesis of psoriasis as the dysregulation of immu- nity triggered by environmental and genetic stimuli. Psoriasis was originally regarded as a primary disorder of epidermal hyperproliferation. However, experimental models and clinical results from immunomodulating therapies haverefined this perspective in conceptualizing psoriasis as a genetically pro- grammed pathologic interaction between resident skin cells, infiltrating immunocytes and a host of proinflammatory cytokines, chemokines and growth factors produced by these immunocytes. The main focus of this volume will be the evolving paradigm of therapy for psoriasis. The first segment of the volume provides a background for the dis- ease. The first two chapters will review the history of psoriasis and psoriasis therapy, and the pathophysiology of psoriasis. The third chapter provides a detailed clinical reviewof psoriasis and psoriatic arthritis. The review of therapy begins in the next segment of the volume. Chapters 4 and 5 review the myriad of topical therapies available for psoriasis, and Chapter 6 discusses the spectrum of ultraviolet therapies and novel laser ther- apies for the treatment of this condition. Prior to the advent of biologic thera- pies, a number of oral therapies were the mainstay of systemic treatment for psoriasis. The efficacy and safety of these agents will be reviewed in Chapters 7and 8. Over the last few years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. Chapter 9 will review biologic therapy for psoriasis, providing an overview of infliximab, etanercept, adali- mumab,efalizumab,and alefacept. Biologic and oral therapies in development will be discussed in Chapter 10. Psoriasis-related quality of life is a broad term that aims to incorporate the physical, psychosocial, and economic implications of the disease, and their cumulativeimpact on the patient. The final chapter will address the important topic of quality of life issues in psoriasis. The treatment of psoriasis is truly an evolving field. In the volume,an out- standing group of authorshaveprovided the most recent clinical data,encom- X Preface passing proper applications,efficacy,and safety. We hope that you will find the information useful in the scope of your research or practice. We urge you, however,to keep abreast of this field after reading this volume,as the flow of new information is constant. Jeffrey M. Weinberg,MD New York,August 2007 Treatment of Psoriasis 1 Edited by J.M. Weinberg ©2008 Birkhäuser Verlag/Switzerland Introduction: History of psoriasis and psoriasis therapy Alissa Cowden and Abby S. Van Voorhees University of Pennsylvania,Philadelphia,PA 19104,USA Introduction This chronicle of psoriasis begins in ancient times when psoriasis,leprosy,and other inflammatoryskin disorders were thought to be the same condition. The identification of psoriasis as a distinct entity did not occur until the 19th century, when clinical descriptions distinguished it from other cutaneous dis- orders. Histopathologic descriptions in the 1960s and 1970s shed some light on the pathophysiology of psoriasis, but many aspects of the disease remain unknown to this day.As Bechet expressed, “Psoriasis is an antidote for der- matologists’ego”[1]. Given the lack of understanding of its pathophysiology,early psoriasis ther- apies werediscovered serendipitously. Chance observations by early clinicians of psoriatic improvement in patients prescribed medications for other condi- tions led to advancements in therapy. As our understanding grew, this serendipity evolved into detailed targeting of specific immunological process- es. These newly directed therapies clarified aspects of the pathophysiology and treatment of psoriasis and other immune-mediated diseases. Ancient history:Lepra,psora,psoriasis The roots of the identification of psoriasis lie in Ancient Greece. The Greeks, who pioneered the field of medicine, divided skin disease into the categories of psora,lepra andleichen[2]. Psora referred to itch,while leprawas derived from the Greek words lopos (the epidermis) and lepo (to scale) [3]. Hippocrates (460–377 BC) was one of the first authors to write descriptions of skin disorders. He utilized the word lopoi to describe the dry, scaly, disfigur- ing eruptions of psoriasis,leprosy,and other inflammatory skin disorders [4]. Similar to Hippocrates’ works, the Old Testament also lumped together many cutaneous disorders. The biblical term tsaraat, or zaraath, described a range of skin conditions including leprosy and psoriasis. Lepers were often