Mild-to-Moderate Psoriasis

DK5988_title 6/22/06 10:21 AM Page 1

Mild-to-Moderate

PSORIASIS John Y. M. Koo University of California San Francisco Medical Center San Francisco, California, U.S.A.

Mark G. Lebwohl Mount Sinai School of Medicine New York, New York, U.S.A.

Chai Sue Lee University of California Davis Medical Center Sacramento, California, U.S.A.

New York London

Informa Healthcare USA, Inc. 270 Madison Avenue New York, NY 10016 © 2006 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8493-3723-2 (Hardcover) International Standard Book Number-13: 978-0-8493-3723-9 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright. com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Informa Web site at www.informa.com and the Informa Healthcare Web site at www.informahealthcare.com

Preface Preface

The goal of this book is to provide guidance on state-of-the-art clinical management of mild-to-moderate psoriasis, utilizing the experiences of a group of experts well known in the psoriasis field. The treatments covered include topical corticosteroids, calcipotriene, tazarotene, tar, anthralin, salicyclic acid, phototherapy, and lasers. There is a chapter highlighting recent advances in combination therapy. We have also included chapters on palmar plantar psoriasis, scalp psoriasis, inverse psoriasis, and nail psoriasis because these are areas of the body that are frequently resistant to ordinary forms of therapy. The editors are hopeful that the comprehensive yet practical and problem-focused approach to the management of mild-tomoderate psoriasis makes this a reference that dermatologists, primary care physicians, residents, medical students, and other health care professionals can turn to again and again for the most updated guidance in taking care of patients with mild-to-moderate psoriasis. John Y. M. Koo Mark G. Lebwohl Chai Sue Lee

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Contents

Preface . . . . iii Contributors . . . . xiii 1. Therapy of Mild-to-Moderate Psoriasis—Introduction . . . . . 1 Mark G. Lebwohl 2. General Approach to Psoriasis Treatment . . . . . . . . . . . . . . 3 Steven R. Feldman Introduction . . . . 3 General Considerations in Treatment of Localized Psoriasis . . . . 5 Conclusions . . . . 6 Reference . . . . 7 3. The Koo–Menter Psoriasis Instrument for Identifying Candidate Patients for Systemic Therapy . . . . . . . . . . . . . . 9 John Y. M. Koo, Jonathan W. Kowalski, Mark G. Lebwohl, Chris M. Kozma, and Alan Menter Introduction . . . . 9 Overview . . . . 10 Components of the Koo–Menter Psoriasis Instrument . . . . 10 Background on the PQOL-12 . . . . 14 Application of the Original PQOL . . . . 14 Development of the PQOL-12 . . . . 15 v

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Study 1: Multicentered Office-Based Study . . . . 15 Study 2: Using Data from the Randomized Clinical Trial . . . . 24 Minimally Important Difference . . . . 26 Test–Retest Reliability of the PQOL-12 . . . . 26 Calculating the PQOL-12 Score Within the KMPI . . . . 26 Discussion on KMPI . . . . 27 Conclusion . . . . 27 References . . . . 28 4. General Guidelines for Administration of Topical Agents in the Treatment of Mild-to-Moderate Psoriasis . . . . . . . . Jashin J. Wu and Gerald D. Weinstein Factors of Psoriasis . . . . 30 Medications . . . . 32 References . . . . 38

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5. Topical Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . 41 Jason Givan, Daniel Pearce, and Steven R. Feldman Introduction . . . . 41 Rationale for Psoriasis Therapy . . . . 42 Mechanism of Action and Biologic Potency . . . . 42 Delivery and Physiologic Potency . . . . 44 Adherence . . . . 46 Lessons from Skin Cap1 . . . . 48 Efficacy . . . . 49 Safety . . . . 50 Safer Topical Corticosteroids: Are They Possible? . . . . 51 Cost Considerations . . . . 52 Practical Use of Topical Corticosteroids . . . . 52 Steroid Alternatives: Complementary, Not Really Alternatives . . . . 53 Summary . . . . 54 References . . . . 55 6. Vitamin D3 Analogs . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chai Sue Lee and John Y. M. Koo Chemistry and Mechanism of Action . . . . 60 Calcipotriene Monotherapy . . . . 61 Calcipotriene in Children . . . . 61

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Calcipotriene vs. Other Topical Agents . . . . 62 Combination Therapy . . . . 63 Calcipotriene and Topical Steroids . . . . 63 Calcipotriene and Tazarotene . . . . 64 Calcipotriene and Phototherapy . . . . 64 Calcipotriene and Systemic Agents . . . . 65 Adverse Effects . . . . 66 Calcipotriene Application in Psoriasis . . . . 69 Conclusions . . . . 70 References . . . . 70 7. Fixed-Dose Corticosteroid/Calcipotriene Combination Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Chai Sue Lee and John Y. M. Koo Combination Corticosteroid/Calcipotriene Therapy . . . . 76 Clinical Trials and Analyses of Fixed-Combination Formulation of Betamethasone Dipropionate/Calcipotriene . . . . 77 The Fixed-Dose Combination Is More Effective Than Steroid or Calcipotriene Monotherapy . . . . 77 The Fixed-Dose Combination b.i.d. Achieves Greater PASI Reduction Within One Week vs. Steroid Monotherapy . . . . 77 Once-Daily Fixed-Dose Combination Is Safe and Effective . . . . 78 Once-Daily Fixed-Dose Combination Is as Safe and Effective as b.i.d. Therapy . . . . 80 Once-Daily Fixed-Dose Therapy Achieves Higher Clearance and Fewer Adverse Events vs. Monotherapy . . . . 81 Once-Daily Fixed-Dose Therapy Is Effective for Patients with Mild, Moderate, and Severe Psoriasis . . . . 81 Investigators and Patients’ Assessments of Once-Daily Fixed-Dosed Therapy Agree . . . . 82 Long-Term, Once-Daily Fixed-Dose Therapy Is Safe and Effective . . . . 83 Potential Benefits of Fixed-Dose Combination Therapy . . . . 84 In Combination with Biologics . . . . 86 In Combination with Other Systemic Agents . . . . 87 Potential Effects on Compliance . . . . 87

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Conclusions . . . . 87 References . . . . 88 8. Tazarotene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chai Sue Lee and John Y. M. Koo Chemistry and Mechanism of Action . . . . 91 Tazarotene Monotherapy . . . . 93 Tazarotene vs. Topical Steroids . . . . 93 Combination Therapy . . . . 94 Tazarotene and Topical Steroids . . . . 94 Tazarotene and Topical Steroid-Induced Skin Atrophy . . . . 96 Tazarotene Chemical Compatibility with a Topical Steroid . . . . 96 Tazarotene and Calcipotriene . . . . 97 Tazarotene and UVB Phototherapy . . . . 97 Tazarotene and PUVA Phototherapy . . . . 98 Tazarotene and Nail Psoriasis . . . . 99 Tazarotene Application in Psoriasis . . . . 99 Side Effects . . . . 100 Conclusions . . . . 101 References . . . . 101 9. Topical Calcineurin Inhibitors . . . . . . . . . . . . . . . . . . . . Patricia Tinio and Mark G. Lebwohl Mechanism of Action . . . . 107 Clinical Properties . . . . 107 References . . . . 111 10. Treatment of Mild-to-Moderate Psoriasis with Coal Tar, Anthralin, Salicylic Acid, and Lactic Acid . . . . . . . . . . . Priya Sivanesan and John Y. M. Koo Coal Tar . . . . 115 Anthralin . . . . 119 Salicylic Acid . . . . 121 Lactic Acid . . . . 122 Conclusion . . . . 122 References . . . . 122

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11. Phototherapy and Laser for the Treatment of Mild-to-Moderate Psoriasis . . . . . . . . . . . . . . . . . . . Holly A. Kerr, Henry W. Lim, and Jennifer Trepte Introduction . . . . 125 Mechanism of Action . . . . 126 Ultraviolet B . . . . 126 Psoralen and UVA . . . . 131 Targeted (Localized) Phototherapy . . . . 137 Ultraviolet A1 . . . . 141 Conclusion . . . . 142 References . . . . 143

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12. Combination Therapy . . . . . . . . . . . . . . . . . . . . . . . . . 147 Wendy Myers, Jennifer Tan, and Alice B. Gottlieb The Rationale for Combination Therapy . . . . 147 Phototherapy Combinations . . . . 148 UV Phototherapy and Topical Medications . . . . 150 Combining Systemic Agents with Topical Therapies in the Treatment of Mild-to-Moderate Psoriasis . . . . 154 Future Therapies for the Combination Treatment of Mild-to-Moderate Psoriasis . . . . 158 References . . . . 159 13. Topical Sequential Therapy of Psoriasis . . . . . . . . . . . . . John Y. M. Koo and Shanthi M. Colaco Introduction . . . . 163 Topical Sequential Therapy: Calcipotriene and Halobetasol Propionate . . . . 164 Optimal Timing to Proceed Down Sequential Therapy Scheme . . . . 167 Sequential Therapy as a Flexible Therapeutic Strategy . . . . 168 Sequential Therapy with New Topical Steroid Formulations . . . . 168 Topical Sequential Therapy Possibilities Beyond Calcipotriene . . . . 169 References . . . . 170

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14. New Developments in Topical Psoriasis Therapy . . . . . . . Chai Sue Lee, John Y. M. Koo, and Shanthi M. Colaco Introduction . . . . 173

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Clobetasol Propionate Spray (Clobex Spray) . . . . 174 Clobetasol Propionate Shampoo (Clobex Shampoo) . . . . 175 Clobetasol Proprionate Lotion (Clobex Lotion) . . . . 176 Hydrogel Patch . . . . 176 Conclusions . . . . 181 References . . . . 181 15. Palmoplantar Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . Brian Bonish and Kenneth B. Gordon Treatment . . . . 185 Topical Therapy . . . . 185 Phototherapy . . . . 188 Systemic Therapy . . . . 189 Biologic Therapies . . . . 190 Summary: A Treatment Approach for Therapy of Palmoplantar Psoriasis . . . . 190 Conclusion . . . . 192 References . . . . 192

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16. Scalp Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Peter C. M. van de Kerkhof, Marloes M. Kleinpenning, and Rianne M. J. P. Gerritsen Introduction . . . . 195 Epidemiology . . . . 195 Clinical Morphology . . . . 196 Differential Diagnosis . . . . 197 General Therapeutic Aspects . . . . 197 Shampoos . . . . 198 Descaling of the Scalp . . . . 199 Coal Tar and Dithranol . . . . 199 Imidazole Antifungals . . . . 199 Topical Corticosteroids . . . . 200 Vitamin D3 Analogs . . . . 201 Phototherapy . . . . 202 Systemic Treatments . . . . 202 Treatment Strategies in Scalp Psoriasis . . . . 202 Conclusion . . . . 203 References . . . . 203

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17. Inverse Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Robert A. Lee and Abby S. van Voorhees Introduction . . . . 207 Epidemiology . . . . 207 Clinical Presentation . . . . 208 Etiology . . . . 209 Differential Diagnosis . . . . 209 Management . . . . 210 Conclusion . . . . 217 References . . . . 217

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18. Psoriasis of the Nails . . . . . . . . . . . . . . . . . . . . . . . . . . Maithily A. Nandedkar-Thomas and Richard K. Scher Introduction . . . . 221 Manifestations of Nail Psoriasis . . . . 222 Association with Psoriatic Arthritis . . . . 226 Associated Genetic Haplotypes . . . . 228 Nail Psoriasis: Childhood vs. Adult Onset . . . . 228 Diagnostic Challenge: Isolated Nail Psoriasis and Its Impersonators . . . . 229 Diagnostic Procedure: The Nail Biopsy . . . . 231 Measurement of Severity: The Nail Psoriasis Severity Index . . . . 231 Treatment Options and Complications from Therapy . . . . 231 References . . . . 237

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19. Summary of Therapeutic Options for Mild-to-Moderate Psoriasis . . . . . . . . . . . . . . . . . . . . . Cindy Berthelot, Jennifer Clay Cather, and Alan Menter Introduction . . . . 243 Topical Therapies . . . . 245 Phototherapy . . . . 256 Summary . . . . 257 References . . . . 257 Index . . . . 263

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Contributors

Cindy Berthelot University of Texas Medical School Southwestern, Dallas, Texas, U.S.A. Brian Bonish Division of Dermatology, Stritch School of Medicine, Loyola University, Maywood, Illinois, U.S.A. Jennifer Clay Cather Division of Dermatology, Baylor University Medical Center, Dallas, Texas, U.S.A. Shanthi M. Colaco Department of Dermatology, Psoriasis and Skin Treatment Center, University of California San Francisco Medical Center, San Francisco, California, U.S.A. Steven R. Feldman Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, U.S.A. Rianne M. J. P. Gerritsen Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands Jason Givan Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, U.S.A. Kenneth B. Gordon Feinberg School of Medicine, Evanston Northwestern Healthcare and Northwestern University, Skokie, Illinois, U.S.A.

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Alice B. Gottlieb Department of Dermatology, Tuffs-New England Medical Center, Boston, Massachusetts, U.S.A. Holly A. Kerr Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, U.S.A. Marloes M. Kleinpenning Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands John Y. M. Koo Department of Dermatology, Psoriasis and Skin Treatment Center, University of California San Francisco Medical Center, San Francisco, California, U.S.A. Jonathan W. Kowalski Global Health Outcomes Research, Allergan Inc., Irvine, California, U.S.A. Chris M. Kozma University of South Carolina, Columbia, South Carolina, U.S.A. Mark G. Lebwohl Department of Dermatology, Mount Sinai School of Medicine, New York, New York, U.S.A. Chai Sue Lee Department of Dermatology, University of California Davis Medical Center, Sacramento, California, U.S.A. Robert A. Lee Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. Henry W. Lim Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, U.S.A. Alan Menter Division of Dermatology, Baylor University Medical Center, Dallas, Texas, U.S.A. Wendy Myers Department of Medicine, Division of Clinical Pharmacology, Robert Wood Johnson Medical School, New Brunswick, New Jersey, U.S.A. Maithily A. Nandedkar-Thomas Reston, Virginia, U.S.A.

Professional Dermatology Care, PC,

Daniel Pearce Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, U.S.A.

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Richard K. Scher Department of Dermatology, Columbia University Medical Center, New York, New York, U.S.A. Priya Sivanesan Department of Dermatology, University of California San Francisco, San Francisco, California, U.S.A. Jennifer Tan Department of Medicine, Division of Clinical Pharmacology, Robert Wood Johnson Medical School, New Brunswick, New Jersey, U.S.A. Patricia Tinio Department of Dermatology, Mount Sinai School of Medicine, New York, New York, U.S.A. Jennifer Trepte Department of Dermatology, Wayne State University, Detroit, Michigan, U.S.A. Peter C. M. van de Kerkhof Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands Abby S. van Voorhees Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. Gerald D. Weinstein Department of Dermatology, University of California, Irvine, California, U.S.A. Jashin J. Wu Department of Dermatology, University of California, Irvine, California, U.S.A.

1 Therapy of Mild-to-Moderate Psoriasis—Introduction Mark G. Lebwohl Department of Dermatology, Mount Sinai School of Medicine, New York, New York, U.S.A.

The therapy of mild-to-moderate psoriasis has come a long way from the days of tar and anthralin, though the latter treatments are still occasionally used. The introduction of topical corticosteroids in the latter third of the 20th century had a dramatic impact on the topical therapy of psoriasis, and topical corticosteroids remain one of the most important treatments available for mild to moderate disease. Because superpotent corticosteroids are associated with hypothalamic–pituitary–adrenal axis suppression, recent innovations in topical corticosteroid development have emphasized more cosmetically elegant vehicles rather than more potent medications. Most recently, the superpotent corticosteroid clobetasol propionate has been developed in foam, spray, lotion, and shampoo vehicles. Corticosteroids are also available in creams, emollient creams, ointments, solutions, gels, and even tapes. Therefore it should not be surprising that corticosteroids are extensively covered in this book and controversies such as tachyphylaxis as well as issues such as compliance with therapy are raised by experts in the field. A major breakthrough in the treatment of mild to moderate psoriasis occurred with the introduction of vitamin D analogs. Calcipotriene, also known as calcipotriol, was the first agent approved and it was followed by additional vitamin D analogs including tacalcitol, calcitriol, and others.

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Tazarotene, a retinoid developed for psoriasis, was the next class of agent to be developed for this disease. Other topical agents include the topical immunomodulators, pimecrolimus, and tacrolimus. These agents are not very effective on thick plaques of the elbows and knees, but are highly effective on facial and intertriginous skin, precisely those areas where use of topical corticosteroids is associated with the development of cutaneous atrophy and formation of striae and telangiectasia. All of the above agents are reviewed comprehensively in chapters written by leading authorities. What can the clinician do when monotherapy with topical agents is not sufficiently effective but the disease is not severe enough to justify systemic therapy? Combination therapy has proven to be more effective than monotherapy with selected agents. Moreover, combination therapy often eliminates the side effects of monotherapy. For example, the combination of topical corticosteroids and tazarotene is not only more effective than either treatment alone, but tazarotene protects against the atrophy of the corticosteroid while the corticosteroid minimizes the irritation caused by tazarotene. Likewise, the combination of calcipotriene with topical corticosteroids is more effective than either agent alone, allowing reduced use of the corticosteroid and less irritation caused by the calcipotriene. The use of combination therapy has led to the development of yet another new agent that combines calcipotriene with betamethasone dipropionate. When combination therapy is not adequate, use of intralesional corticosteroids may be effective, and when the latter is not sufficient, phototherapy may be warranted. New forms of phototherapy including narrowband ultraviolet B (UVB) and localized targeted high output phototherapy such as that afforded by the excimer laser are often effective for localized refractory plaques of psoriasis. Finally, unique body sites such as the nails or scalp may require different vehicles and approaches to achieve good results. All of these challenges are addressed by experts in Therapy of Mild-to-Moderate Psoriasis with the hope that our patients will benefit from this book.

2 General Approach to Psoriasis Treatment Steven R. Feldman Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, U.S.A.

INTRODUCTION Psoriasis is a complex disease to manage. It may present with wide ranging severity affecting vastly different parts of the body. Very limited areas to very diffuse generalized disease can be present, and the character of the lesions may vary from minimal redness to thick scaly red plaques. The various presentations add to the complexity in choosing treatment. Adding to the complexity of the treatment is the availability of a host of different topical, phototherapy, and systemic treatment options. Matching the appropriate treatment with the presentation of the disease is an art. Adding to the complexity of this art is the fact that it is not just lesions that are being treated, but a patient, and patients’ responses to the lesions also vary considerably. Patients also differ in their concern about side effects and the way they tolerate different topical preparations. These variations can be dramatic. In nearly all patients, psoriasis impacts quality of life, including social interactions. The overall impact of psoriasis on quality of life—particularly the effect of psoriasis on social interactions—must also be addressed. Step I: Address Patients’ Psychosocial Needs The first step in managing all patients with psoriasis is to address their psychosocial needs. This is fundamental to effective psoriasis treatment. 3

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Addressing psychosocial issues helps to establish a strong working relationship between the physician and the patient. By doing so, patients are likely to be more compliant with treatment and should have better health outcomes. The first step to managing psychosocial needs is to sit within touching distance of the patient. While examining the lesions and talking to the patient, the physician should palpate lesions. While doing so the physician can remark, ‘‘Wow, these lesions are really thick.’’ The purpose of the palpation is not to determine the thickness of the lesions; the purpose of touching the lesions is to communicate to patients that they are not untouchable. Patients with psoriasis feel isolated from others because of their disease and by touching the lesions the physician communicates to the patient that they should not be afraid of having contact with other people. Dr. J. Lamar Calloway, long-time dermatologist at Duke University, would actually rub his own face after palpating the psoriasis to help communicate to patients that psoriasis is not an infectious condition. While sitting close to the patient, the physician should also proactively ask patients a few questions about their disease. These questions are not likely to change what the physician will prescribe, but they may change how the patient views the doctor and the prescription and ultimately how adherent the patient will be to the treatment recommendations. There are many things about psoriasis that are bothersome to patients and asking questions about a few of these helps communicate to the patient that the dermatologist understands the disease and what the patient is going through. One might ask if the itching has been bothersome, if past treatments have been messy or ineffective, or if psychosocial concerns have been an issue. Simply asking a few questions (and listening intently) helps further the bond between the physician and the patient. No healthcare provider has enough time to explain to patients everything they would like to know about psoriasis. All of us, however, have the time to encourage patients to join the National Psoriasis Foundation. The Psoriasis Foundation provides numerous benefits to patients. First, it helps patients feel a part of a group, reducing their sense of isolation due to the disease. Second, the Foundation helps educate patients about available treatment options. Third, the Foundation encourages patients to be compliant with their dermatologists’ recommendations. Fourth, the Psoriasis Foundation empowers patients to work towards a cure for the disease. The Psoriasis Foundation offers a variety of brochures that are very useful for educating patients about specific treatment options. The Psoriasis Foundation periodical for patients entitled ‘‘Psoriasis Advance’’ helps patients answer many of the psychosocial issues that physicians may not feel comfortable addressing; for example, what to do if the lifeguard says you cannot go in the pool, what to do when people point and ask questions, or other social situations. Communication among members is very supportive. Patients can be encouraged to join the Psoriasis Foundation by simply

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visiting the web sitea, writing to the foundationb, or callingc. Anyone can join, even without paying, though there is a recommended donation of $27 (to cover mailing costs). Step II: Categorization of Psoriasis Once psychosocial issues are addressed, further treatment planning is dependent on determining whether patients have relatively localized disease suitable for topical therapy or more extensive disease where phototherapy or systemic treatments will be used. This book focuses on the treatment of people with relatively localized disease. Formerly, the common categorization scheme of mild, moderate, and severe psoriasis has been used. These three categories do not correspond well to treatment decision making, however. Typically, one would hear categorizations of mild-to-moderate versus moderate-to-severe psoriasis for treatment purposes. Mild-to-moderate psoriasis tends to refer to patients with relatively localized psoriasis. The moderate-to-severe category tends to refer to the patient with more generalized disease or disease that is otherwise disabling. Treatment of this latter group has been covered in an excellent textbook entitled ‘‘Therapy of Moderate to Severe Psoriasis’’ by Weinstein and Gottlieb (1). This chapter and this book focus on the treatment of the patient with mild-to-moderate or localized psoriasis. GENERAL CONSIDERATIONS IN TREATMENT OF LOCALIZED PSORIASIS The treatment of localized psoriasis focuses on local treatments, predominately topical treatments, although certainly localized phototherapy is also used. When it comes to topical treatments, multiple agents are available including tar, anthralin, topical corticosteroids, topical vitamin D and Vitamin A analogues, topical immunomodulators (tacrolimus and pimecrolimus), and keratolytics (such as salicylic acid). Whichever of these agents are chosen, a primary consideration determining patients’ outcomes will be patients’ compliance with the topical treatment regimen. When patients with psoriasis have been asked about their compliance with topical therapy, approximately 40% reported noncompliance. In a clinical trial that assessed compliance using both patient diaries and electronic monitors, patients vastly overstated their true compliance. It is clear that patients are not truthful with their doctors about their compliance with topical therapy. Topical therapy is time consuming and messy, and over time, compliance to topical therapy decreases. Indeed, chronic diseases like a

www.psoriasis.org 6600 SW 92nd Avenue, Suite 300, Portland, OR 97223-7195, U.S.A. c 1-800-723-9166 b

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psoriasis—as well as treatment of the chronic condition—are frustrating and wear on people over time. Outcomes of localized psoriasis treatment can be improved by encouraging patients to be compliant. There are a number of things that physicians can do to improve a patient’s compliance. First, as discussed above, physicians should establish a strong working relationship with the patient. They should involve the patient in the treatment-making decision. Vehicles which the patients do not mind applying should be chosen. While it was commonly thought that ointments are more effective, new non-ointment, less messy vehicles may be able to deliver active drugs just as well as traditional ointments, and better compliance with a non-messy product may actually lead to greater efficacy than is seen with ointments. Patients are also reluctant to apply topical therapy for long periods of time before they see improvement. Fast acting agents should be used, especially initially. The sequential therapy approach consists of using stronger, faster acting but potentially more risky treatments early in the course of therapy and then transitioning to lower acting but safer treatments for the long-term maintenance of the disease. This approach has the advantage of helping patients see early in the course of therapy that treatments work, thereby improving patients’ compliance. Other approaches are to use the stronger topical agents such as clobetasol-containing topical corticosteroid products initially and then using them intermittently as needed to control the disease. Another way to help improve compliance is to encourage patients to return to the office or at least contact the physician shortly after treatment has begun, for example in one to two weeks. A long interval before a return visit may lead to poor compliance if the patient feels that it will be impossible to be compliant for that length of time. By seeing patients back in just a week, patients are more likely to comply with therapy over that week, thereby seeing the potential benefits the treatment offers. Once they have seen that the treatment actually works, they will use the treatment intermittently knowing that it will be effective for them. This short interval between treatment and the return visit may be especially important for patients with scalp psoriasis, as compliance with topical scalp treatment regimens is exceedingly time consuming and difficult. CONCLUSIONS Treating mild-to-moderate psoriasis (relatively localized psoriasis) can be frustrating for both the patient and the physician. Much of this frustration can be elevated by addressing patients’ psychosocial concerns up front. All patients with psoriasis should be encouraged to join the National Psoriasis Foundation. This helps reduce patients in isolation and increase their knowledge about treatments, ultimately resulting in approved compliance with the physician-recommended treatment regimens.

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Topical treatments are proven for most patients with mild-to-moderate psoriasis. Getting patients to actually use the treatment is a critical component in maximizing topical treatment efficacy. Patients should be encouraged to participate in the treatment planning process, choosing vehicles and other treatment characteristics (such as dosing) that fit the patient’s lifestyle. Using rapidly acting agents initially and encouraging patients to come in for an early follow-up visit or other factors may help improve the compliance. The resulting improvement should help reduce the frustration of psoriasis on both the patient and the physician. ACKNOWLEDGMENTS Center for Dermatology Research is funded by a grant from Galderma Laboratories, LP. Dr. Feldman has also received support from Connetics, Astellas, Abbott, Amgen, Biogenidec, Centocor, Photomedex, and Genentech. REFERENCE 1. Weinstein GD, Gottlieb AB. Therapy of moderate to severe psoriasis. In: revised and expanded. 2d ed. New York, NY: Marcel Dekker, 2003.

3 The Koo–Menter Psoriasis Instrument for Identifying Candidate Patients for Systemic Therapy John Y. M. Koo Department of Dermatology, Psoriasis and Skin Treatment Center, University of California San Francisco Medical Center, San Francisco, California, U.S.A.

Jonathan W. Kowalski Global Health Outcomes Research, Allergan Inc., Irvine, California, U.S.A.

Mark G. Lebwohl Department of Dermatology, Mount Sinai School of Medicine, New York, New York, U.S.A.

Chris M. Kozma University of South Carolina, Columbia, South Carolina, U.S.A.

Alan Menter Division of Dermatology, Baylor University Medical Center, Dallas, Texas, U.S.A.

INTRODUCTION According to a National Psoriasis Foundation survey, 78% of members with severe psoriasis reported frustration with the efficacy of their current treatment and 32% indicated that the treatment they are receiving is not aggressive enough (1). In addition, 87% of all psoriasis patients were receiving

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only topical medications for their psoriasis and only 26% of patients were very satisfied with their treatments. Several highly effective systemic therapies for psoriasis already exist and other potential new systemic therapies are in development for patients with psoriasis. Most psoriasis opinion leaders feel that a greater percentage of the total psoriasis population can benefit from the use of systemic agents. What may be needed is an instrument to assist in the critical decision of whether therapy that is more aggressive may be needed or not. There has been no convenient tool that can assist dermatologists in identifying patients who would benefit from systemic therapy for psoriasis and at the same time justify these decisions to third-party payers. However, tools such as these exist for other chronic diseases treated by rheumatologists (e.g., for rheumatoid arthritis) and urologists (e.g., for benign prostatic hyperplasia). Such a tool for psoriasis would need to incorporate both the assessments of health-related quality-of-life and the other measures of disease severity and associated joint disorder (2). The Koo–Menter Psoriasis Instrument (KMPI) has been designed to be a practical assessment tool, which dermatologists can quickly and easily use in their daily practice to help guide them in identifying patients with psoriasis who may be candidates for systemic therapy. OVERVIEW The KMPI is a two page questionnaire on a single sheet (Figs. 1 and 2). On the front page, the patient completes three brief sections while awaiting evaluation by the physician. The topics of these sections include: validated psoriasis-specific quality-of-life, parts of body currently affected by psoriasis, and psoriatic arthritis/joint symptomatology. The physician then completes the reverse side of the instrument during the physical examination. The quality-of-life score is easily totaled from the front page; body surface area (BSA) involvement is assessed using the ‘‘rule of nines,’’ and a series of simple ‘‘yes’’ or ‘‘no’’ questions allows the physician to quickly characterize the patient’s disease and treatment history. The physician uses the psoriasis-specific quality-of-life score, the total percentage of BSA involvement, and the overall clinical assessment of the patient’s psoriasis to determine the need for systemic therapy. COMPONENTS OF THE KOO–MENTER PSORIASIS INSTRUMENT Patient Self Assessment Part 1. Health-Related Quality of Life The patient completes the 12-item Psoriasis Quality-of-Life Questionnaire (PQOL-12).

Koo–Menter Psoriasis Instrument

Figure 1 Koo-Menter psoriasis instrument; patient self-assessment.

11

12

Figure 2 Koo-Menter psoriasis instrument; physician assessment.

Koo et al.

Koo–Menter Psoriasis Instrument

13

Developed from the original 41-item PQOL (which was created a decade ago based on literature review, patient focus groups and pilot testing in 505 patients with psoriasis), the items from the PQOL-12 were identified using new data from 474 patients with psoriasis and determined to be valid and reliable in assessing the impact of psoriasis on patients across the spectrum of psoriasis severity. In addition, the items of the PQOL-12 are responsive and sensitive in measuring clinically meaningful change and improvement following treatment. The PQOL-12 was chosen as the quality-of-life measure for the KMPI because of its brevity, broad applicability across disease severity, the rigor of its development and psychometric validation, and its psoriasis-specific focus. The validation data for PQOL-12 will be described later under the section ‘‘Background on the 12-item PQOL-12.’’ Part 2. Patient Indication of Psoriasis Sites The Patient indicates the location of their psoriatic lesions by placing ‘‘X’s’’ on figures illustrating the front and back of the human body. The patient’s indication of psoriasis sites helps facilitate the physician’s evaluation of the area of psoriatic involvement in the patient. Part 3. Joint Symptoms The patient answers four questions about joint symptoms and psoriatic arthritis. These items, developed based on feedback from leading arthritis experts, are included to facilitate early detection of this important associated condition while ensuring that the decision for systemic therapy is also based on joint symptomatology. Physician Assessment Part 1. Total Quality-of-Life Assessment Score The physician totals the patient’s quality-of-life score from the front page. Part 2. Area of Involvement The physician calculates the patient’s BSA involvement using the rule of nines or by the estimation using the area of open hand as approximately 1% of the total body surface. Part 3. Assessment of Psoriasis Severity The following severity criteria are then assessed by the physician using simple ‘‘yes’’ or ‘‘no’’ options:



Plaque, erythrodermic or pustular psoriasis with more than 10% BSA involvement Guttate psoriasis

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Koo et al.


Localized psoriasis (less than 10% BSA involvement) that is resistant to topical therapy or is disabling (e.g., palmarplantar psoriasis)
One of the serious subtypes of localized psoriasis (less than 10% BSA involvement) that has a possibility of progression (e.g., generalized pustular or erythrodermic psoriasis), or
Clinical evidence of psoriatic joint disease as assessed by the patient and physician. Part 4. Feasibility of Phototherapy Lastly, the feasibility and clinical appropriateness of phototherapy is rapidly evaluated in six simple questions. Determination of Candidacy for Systemic Therapy Using the responses to the ‘‘yes’’ or ‘‘no’’ questions in Part 3 and Part 4 of the Physician Assessment, the candidacy for systemic therapy is determined. If the physician has checked at least one of the shaded boxes in both Part 3 and Part 4, then the patient is a candidate for systemic therapy.

BACKGROUND ON THE PQOL-12 The PQOL-12 is a valid and reliable subset of the original PQOL, a 41-item, self-administered, disease-specific questionnaire initially developed in 1991 by John Koo, M.D.(3–5). The questionnaire items were generated through focus groups in which patients discussed their experiences with psoriasis. A nationwide, population-based, demographically balanced sample of 50,000 households was then used to identify 599 psoriasis patients in the United States for item testing. The 41-item PQOL was qualitatively divided into two domains: psychosocial and physical. The psychosocial domain consisted of 22 items requiring patients to characterize the impact of psoriasis on their interactions with friends and family and on their feelings and self-perception. The physical domain consisted of 19 items requesting that patients rate the impact of their psoriasis symptoms on their daily activities. PQOL items were rated on an 11-point Likert-type scale where 0 ¼ ‘‘not at all,’’ 5 ¼ ‘‘somewhat,’’ and 10 ¼ ‘‘very much.’’ APPLICATION OF THE ORIGINAL PQOL The 41-item PQOL was utilized in a clinical study of 71 patients with stable plaque psoriasis on up to 20% of their total BSA, and plaque elevation of at least moderate severity (6). Psychometric analysis of the 41-item PQOL showed satisfactory reliability, validity, and responsiveness to change (3). Items within each domain had approximately equal variances and

Koo–Menter Psoriasis Instrument

15

contributed equally to the total score and were, therefore, summed without weighting. The 41-item PQOL was scored by computing the mean score for each domain, on a 0 to 10 scale. DEVELOPMENT OF THE PQOL-12 The 41-item PQOL was too lengthy for frequent use in clinical practice, and the assumption of two domains (psychosocial and physical) was not entirely appropriate as analyses following its development had shown overlap among these domains. A shorter instrument measuring unique constructs was needed for clinicians and researchers who were interested in assessing psoriasis-specific Health-Related Quality-of-Life (HRQOL) in clinical research or daily practice. Factor analysis techniques were used to refine the 41-item PQOL. The resulting questionnaire (PQOL-12) consisted of 12 items measured on one domain. Psychometric properties of the PQOL-12 were assessed using data from an multicentered office-based study (Study 1) and a randomized clinical trial (Study 2). STUDY 1: MULTICENTERED OFFICE-BASED STUDY Item Reduction The PQOL was refined and reduced to a 12-item instrument using data from an office-based study of 483 patients stratified by physician-rated psoriasis severity at three U.S. psoriasis centers from October 2001 to May 2002 (7,8). Severity was assessed by the investigator at the time of enrollment, and included a psoriasis area severity index (PASI) evaluation. Physicians completed several different symptom severity assessment questionnaires: global assessment of severity ranging from mild, moderate, and severe based on the BSA affected, PASI, overall lesional assessment (OLA) and severity of symptoms experienced by patients. In addition, each patient was asked to complete a demographic questionnaire, the PQOL, the Dermatology Life Quality Index (DLQI) and a disease severity assessment. Patient-rated severity was defined as mild, moderate, or severe with the question ‘‘How would you rate the overall severity of your psoriasis, during the past month?’’ For this study, one compound question from the 41-item PQOL [i.e., item #22: How much does your psoriasis interfere with making social contacts and relationships?] in the psychosocial domain was divided into two questions, creating a 42-item instrument. A combination of qualitative review and factor analysis was used to refine the questionnaire. Observations were randomly assigned to an exploratory or confirmatory data set. The exploratory data set (n ¼ 301) was used to reduce and refine the existing PQOL instrument and the confirmatory data set (n ¼ 182) was used to test the reliability of the findings from the exploratory analysis. Each PQOL

16

Koo et al.

item was evaluated for missing values, mean scores, floor/ceiling effects, reading level, translatability, and applicability to all patients. Qualitative criteria were applied by assessing items for redundancy, wording, and meaning/conceptual characteristics. Factor analysis was used to assess the factor structure and item loadings on factors. An item-retention grid consisting of all analytical parameters was created to evaluate all item parameter estimates simultaneously and to facilitate the item-reduction decision process. Once reduced, all analyses performed on the exploratory data set (i.e., descriptive and factor analysis) were repeated on the revised questionnaire (i.e., PQOL-12) using the confirmatory dataset. The confirmatory analyses yielded results consistent with the exploratory analyses. Validity and Reliability Following the confirmatory analysis, the psychometric properties of the PQOL-12 were assessed using Multitrait Analysis Program-Revised for Windows1PC-SAS1–based software7 (9) and the pooled data set (n ¼ 482). The PQOL-12 demonstrated desirable psychometric properties. Ninety-nine percent of respondents completed the survey providing evidence of appropriate item responses of the PQOL-12. The PQOL-12 also exhibited support for the assumptions of summated scales. The PQOL-12 items had approximately equal variances (so they could be summed) and contributed equally to total score (i.e., no weighting needed). All items demonstrated desirable item internal consistency by exceeding the criteria of 0.40 correlation with the total score. The instrument also demonstrated good potential for responsiveness. Cronbach’s a was 0.95 and the mean inter-item correlation was 0.62, providing evidence of reliability (Tables 1 and 2). Although the questionnaire could have been reduced even further, some questions that have been deemed important in clinical practice were retained. Investigation of construct validity indicated that the mean PQOL-12 score was moderately correlated with clinical measures, and highly correlated with patient-rated psoriasis severity (r ¼ 0.61) and with the DLQI (r ¼ 0.78) (Table 3). Individual item correlations with overall patient-rated severity ranged from 0.40 (‘‘how helpless do you feel with regard to your psoriasis?’’) to 0.61 (physical irritation). There were low to moderate correlations with physician-rated severity. A probable explanation for the more modest correlations with physician-rated severity was that physicians based their severity assessment on BSA using an ordinal scale (mild 10%) and lesion morphology that focused strictly on physical characteristics of the patient’s condition. The correlations between individual PQOL-12 items and the DLQI items ranged from 0.50 to 0.69. The total PQOL-12 score was moderately correlated with OLA (0.38), BSA (0.33), and the PASI (0.36), providing evidence of convergent instrument and construct validity. Mean PQOL-12 scores were calculated for each disease severity level by both patients and physicians (Table 4). All pairwise comparisons of

3.45 3.48 3.25 3.25 3.29 3.39

5.76 5.93 5.09 4.24 4.39 4.11

3.41 3.40 3.40 3.84 2.76

3.39

5.60

5.32 4.98 3.84 5.04 5.03

3.28

SD

6.10

Mean

0–10 0–10 0–10 0–10 0–10

0–10

0–10 0–10

0–10

0–10

0–10

0–10

0–10

Range

Abbreviations: PQOL-12; 12-Item Psoriasis Quality-of-Life Questionnaire; SD, standard deviation.

During the past month, how much have each of the following been affected by your psoriasis? Itching? Physical irritation? Physical pain or soreness? Choice of clothing to conceal psoriasis? Mean PQOL-12 Score

Over the past month . . . How self-conscious do you feel with regard to your psoriasis? How helpless do you feel with regard to your psoriasis? How embarrassed do you feel with regard to your psoriasis? How angry or frustrated do you feel with regard to your psoriasis? To what extent does your psoriasis make your appearance unsightly? How disfiguring is your psoriasis? How much does your psoriasis impact your overall emotional well-being? Overall, to what extent does your psoriasis interfere with your capacity to enjoy life?

Item

Study 1 (n ¼ 482)

6.58 5.77 4.23 6.15 5.45

3.63

4.21 4.07

5.31

5.99

6.42

6.51

6.56

Mean

2.76 3.07 3.40 3.48 2.13

3.21

2.95 3.11

2.71

2.91

3.03

2.97

2.71

SD

Study 2 (n ¼ 71)

0–10 0–10 0–10 0–10 0.58–9.42

0–9

0–10 0–10

0–10

0–10

0–10

0–10

0–10

Range

Table 1 Item Descriptive Statistics for the PQOL-12 from an Office-Based Study (Study 1) and the Clinical Trial at Baseline (Study 2)

Koo–Menter Psoriasis Instrument 17

External validity

Construct validity

Validity Item means and variances

Internal consistency reliability

Reliability Internal item consistency

Property

Cronbach’s a ¼ 0.91

Cronbach’s a ¼ 0.95

PQOL-12 score at baseline correlated significantly (p < 0.05) with overall discomfort (0.49), percent BSA

Correlation of items with total score ranged from 0.42 to 0.78

Means of the items were 3.63–6.58 (SD, 2.71– 3.48)

Correlations ranged from 0.42 to 0.78

Study 2 (n ¼ 71)

Correlations ranged from 0.70 to 0.83

Study 1 (n ¼ 483)

Means of the items were Interchangeability of items within 3.84–6.10 (SD, 3.25–3.84) each domain (similar means and variances, so scores can be summed without adjustment) Correlation of items with Relationship of item to domain, total score ranged from assessed by item/domain correlations 0.70 to 0.83 corrected for overlap (similar, moderate item/domain correlations. Items should contribute equally to domain score so that item weighting is unnecessary) Relationship of items to external, PQOL-12 score at baseline often clinical, endpoints (at least correlated significantly (p < 0.05) moderate Spearman correlations) with physician rated severity (0.38), patent rated severity (0.61), overall lesional assessment (0.38), BSA

Extent to which each item correlates with the total score (0.40; 0.30 if domain contains many items) Homogeneity of a domain and extent to which domain is free of random error (Cronbach’s a ¼ 0.70–0.95)

Description/rationale (criterion)

Table 2 Summary of the Psychometric Properties of the 12-Item PQOL in Two Studies

18 Koo et al.

Responsiveness Distribution of responses Item acceptability and comprehension of meaning by respondents (responses should span the majority of the scale) Lack of floor or ceiling Position of initial score effects (initial scores should not be too close to the minimum or maximum values; scales should have sufficient range on either side of the initial score to show improvement or deterioration) Responsive to disease Scores should vary systematically severity across disease severity categories so that milder severity is associated with lower scores than more severe disease

No significant floor (0.0%) or ceiling (0.0%) effects

For physician ratings of severity, there was 1 to 1.5 point difference in scores between mild and severe (p ¼ 0.009), mild and moderate

No significant floor (1.5%) or ceiling (1.0%) effects

For physician ratings of severity, mean PQOL-12 scores were 3.9 for mild, 5.0 for moderate, and 6.4 for severe disease; pairwise comparisons of PQOL-12 means by physician-rated severity groups were

(Continued )

Mean PQOL-12 total score ¼ 5.45, SD ¼ 2.13, Range ¼ 0.58–9.42

affected (0.42), pruritis (0.41), and overall disease severity (0.34); PQOL-12 was not significantly correlated with physician assessment of plaque elevation, scaling, or erythema

Mean PQOL-12 total score ¼ 5.03, SD ¼ 2.76, Range ¼ 0–10

(0.33), PASI (0.36) and the DLQI (0.78)

Koo–Menter Psoriasis Instrument 19

Minimally important difference Difference in scores between improvers vs. those who did not change on measures of severity

Not assessed

Difference for improvers vs. those who showed no change was 1.24 (p < 0.05) on the patientrated severity scale and

(p ¼ 0.08) moderate, and severe disease categories (p ¼ 0.08) at baseline For patient-rated severity, there was 1 to 3 point difference in mean PQOL-12 scores between mild and moderate (p ¼ 0.003), mild and severe (p ¼ 0.001) and moderate and severe (p ¼ 0.03) at baseline Within group change from baseline scores were significantly different with treatment (p < 0.001)

significantly different (p < 0.0002)

For patient-rated severity, mean PQOL-12 scores were 3.2 for mild, 5.2 for moderate, and 7.6 for severe disease; pairwise comparisons were statistically significant (p < 0.0001)

Study 2 (n ¼ 71)

Study 1 (n ¼ 483)

The MID defined as the difference in Not assessed mean change from baseline PQOL-12 score for patients who improved by at least one point on the patient or physician rated severity scale, vs. the

Scores change due to treatment-related improvement

Description/rationale (criterion)

Summary of the Psychometric Properties of the 12-Item PQOL in Two Studies (Continued )

Responsive to treatment

Property

Table 2

20 Koo et al.

The MID defined as the difference in Not assessed mean change from baseline PQOL-12 score for patients who showed at least moderate response to treatment, vs. the mean change from baseline for those who showed only slight response (some improvement—about 25%; however, significant evidence of study condition remains) or no response to treatment (study condition has not changed)

0.39 (p ¼ 0.45) on the physician-rated severity scale Difference for those who showed moderate improvement vs. those who showed no change or only slight improvement on the physicians’ assessment of the global response to treatment was 1.14 (p ¼ 0.18)

Abbreviations: PQOL-12, 12-Item Psoriasis Quality-of-Life Questionnaire; BSA, body surface area; MID, minimally important difference; SD, standard deviation; SE, standard error; Dermatology Life Quality Index; PASI, psoriasis area severity index.

Difference in scores between improvers vs. those who did not change on global evaluation of response to treatment

mean change from baseline for those who showed no change

Koo–Menter Psoriasis Instrument 21

0.44 0.46 0.51 0.54 0.44 0.42

0.23 0.25 0.35 0.41 0.26 0.27

0.58 0.61 0.57 0.49 0.61

0.40

0.20

0.35 0.40 0.33 0.37 0.38

0.48

0.26s

Patient RS (n ¼ 481)

0.41 0.44 0.40 0.33 0.38

0.25

0.36 0.23

0.28

0.29

0.23

0.26

0.25

OLA (n ¼ 480)

0.32 0.34 0.31 0.29 0.33

0.25

0.38 0.26

0.30

0.21

0.20

0.20

0.20

BSA (n ¼ 481)

0.36 0.38 0.36 0.32 0.36

0.26

0.40 0.26

0.30

0.24

0.22

0.22

0.22

PASI (n ¼ 482)

0.62 0.65 0.66 0.68 0.78

0.69

0.66 0.64

0.66

0.58

0.64

0.50

0.64

DLQI (n ¼ 482)

a Spearman correlations for ordinal measurement scales (physician- and patient-rated severity) and Pearson correlations for interval measurement scales (OLA, BSA, PASI, DLQI). Abbreviations: PQOL-12, 12-Item Psoriasis Quality-of-Life Questionnaire; BSA, body surface area; DLQI, dermatology life quality index; OLA, overall lesional assessment; RS, rated severity; PASI, psoriasis area and severity index.

During the past four weeks, how much have each of the following been affected by your psoriasis? Itching? Physical irritation? Physical pain or soreness? Choice of clothing to conceal psoriasis? Mean PQOL-12 Score

In the past four weeks . . . How self-conscious do you feel with regard to your psoriasis? How helpless do you feel with regard to your psoriasis? How embarrassed do you feel with regard to your psoriasis? How angry or frustrated do you feel with regard to your psoriasis? To what extent does your psoriasis make your appearance unsightly? How disfiguring is your psoriasis? How much does your psoriasis impact your overall emotional well-being? Overall, to what extent does your psoriasis interfere with your capacity to enjoy life?

Question

Physician RS (n ¼ 474)

Table 3 Correlationsa Between Final PQOL-12 and Clinical or Other Patient-Reported Measures (Study 1) 22 Koo et al.

Cleared Mild Moderate Severe Cleared Mild Moderate Severe

Severity 0 168 151 155 0 185 178 118

n NA 3.9 (2.6) 5.0 (2.8) 6.4 (2.3) NA 3.2 (2.3) 5.2 (2.3) 7.6 (1.8)

Mean (SD) 0 7 47 17 0 17 35 18

n 0 3.90 5.36 6.36 0 3.59 5.64 6.80

(0) (2.19) (1.89) (2.41) (0) (1.42) (1.99) (1.81)

Mean (SD)

Baseline

Note: Total n < 483 (office-based study) or < 71 (clinical trial) due to missing physician- or patient-rated severity data.

Patient

Physician

Rater

Office-based study (Study 1)

8 38 24 1 1 26 15 5

n

3.35 (1.92) 3.13 (2.21) 4.89 (2.72) 8.00 (NA) 2.25 (NA) 2.38 (1.42) 4.74 (2.26) 6.18 (2.35)

Mean (SD)

End of treatment

Clinical trial (Study 2)

Table 4 Mean PQOL-12 Scores at Baseline and End-of-Treatment, by Physician- and Patient-Rated Severity

Koo–Menter Psoriasis Instrument 23

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PQOL-12 means for both physician and patient ratings of severity in the office-based study were statistically significant (p < 0.001), providing evidence of discriminant validity. Responsiveness The potential for responsiveness was assessed in this office-based crosssectional study (Study 1) using the PQOL-12. The mean score for the PQOL-12 was 5.03 (SD, 2.76). Only 1.5% of the responses were at the floor and 1% of responses were at the ceiling, indicating that the scale has the capability to assess both extremes and that the instrument would be capable of detecting changes during a clinical trial. Responsiveness was further assessed with the following clinical trial data (Study 2). STUDY 2: USING DATA FROM THE RANDOMIZED CLINICAL TRIAL In Study 2, data from the clinical trial on the 41-item PQOL was used to evaluate psychometric properties of the PQOL-12. Disease severity was measured from both physician and patient perspectives. Physicians were asked to evaluate overall patient discomfort, overall disease severity defined as mild, moderate, or severe, percent BSA involvement, signs and symptoms of disease (e.g., pruritis), and overall response to treatment. Patients were asked to complete the 41-item PQOL and an overall evaluation of their disease severity. Patient severity was defined as cleared, mild (trace, mild), moderate (moderate), or severe (severe, very severe) with the question ‘‘How would you rate the overall severity of your psoriasis at this time?’’ The 12 items of the PQOL were used to retrospectively assess validity, reliability, responsiveness, and the minimally important difference (MID) (10) (i.e., a change in the PQOL-12 questionnaire that would indicate the need for a change in therapy). The PQOL-12 demonstrated validity and reliability. Item-to-total correlations were moderate to high, and Cronbach’s a was 0.91. Correlations of the total PQOL-12 score and the individual PQOL-12 items with the clinical measures were moderate for all measures (Table 5). The PQOL-12 also discriminated among physician and patientrated severity at baseline and at end of treatment (Table 4). Responsiveness In Study 2 (using the clinical trial data retrospectively), the responsiveness assessment included examination of floor and ceiling effects, differences in severity levels, and treatment effects. There were no floor or ceiling effects observed for the PQOL-12, indicating that it has the capability to detect improvement and decline in this patient population. Mean PQOL-12 scores

Koo–Menter Psoriasis Instrument

25

Table 5 Spearman Correlations Between PQOL-12 Items and Clinical Measures (Study 2) Question In the past four weeks . . . How self-conscious do you feel with regard to your psoriasis? How helpless do you feel with regard to your psoriasis? How embarrassed do you feel with regard to your psoriasis? How angry or frustrated do you feel with regard to your psoriasis? To what extent does your psoriasis make your appearance unsightly? How disfiguring is your psoriasis? How much does your psoriasis impact your overall emotional well-being? Overall, to what extent does your psoriasis interfere with your capacity to enjoy life? During the past four weeks, how much have each of the following been affected by your psoriasis? Itching? Physical irritation? Physical pain or soreness? Choice of clothing to conceal psoriasis? Mean PQOL-12 Score

Disease discomfort

Disease severity

Percentage BSA

Pruritis

0.34a

0.29a

0.43a

0.30a

0.32a

0.14

0.25a

0.25a

0.35a

0.13

0.30a

0.25a

0.44a

0.19

0.28a

0.28a

0.37a

0.36a

0.36a

0.22

0.31a

0.34a

0.59a

0.18

0.50a

0.32a

0.29a

0.22

0.31a

0.23

0.28a

0.04

0.38a 0.36a 0.31a 0.22

0.22 0.31a 0.28a 0.15

0.16 0.25a 0.17 0.35a

0.67a 0.60a 0.33a 0.22

0.49a

0.34a

0.42a

0.41a

a

Significant at the a ¼ 0.05 level. Abbreviations: PQOL-12, 12-Item Psoriasis Quality-of-Life Questionnaire; BSA, body surface area.

were calculated for each disease severity level by both patients and physicians. Both at the baseline and at the end of treatment, differences between severity levels were generally 1 or 2 points for both physician and patient ratings (Table 4).

26

Koo et al.

MINIMALLY IMPORTANT DIFFERENCE The MID was assessed using an anchor-based approach. The MID is the smallest (or minimal) change in an HRQOL measure that is considered meaningful (or important) by either a clinician or a patient (8). A technique adapted from Juniper et al. was used to calculate the MID using data from Study 2 (8). Three anchors or measures of improvement were investigated including: patient-rated disease severity, physician-rated disease severity, and physician-evaluated global response to treatment. A difference of 1.24 points was observed between those who improved and those who reported no change in the patient-rated severity. The difference in the means of these two groups was statistically significant, indicating an important and statistically significant difference between these two groups. Differences between those who improved and those who did not experience a change was calculated as 1.14 using the physician rating of global response to treatment, although the means were not statistically significant between these two groups. In contrast, differences between physician ratings of severity were smaller (0.39) and the means of improvers and patients who did not experience change were not statistically significant. This finding suggests that a 0.4-point change may be sufficient to distinguish these groups on this measure. In summary, these results suggest that the MID for PQOL-12 score is about 1 point, although it may be as low as 0.4 points. TEST–RETEST RELIABILITY OF THE PQOL-12 Although the above study designs precluded assessment of the test–retest reliability of PQOL-12, preliminary analyses from subsequent research indicate that the test–retest correlation of PQOL-12 exceeds 0.80 when conducted over a period of 2 to 30 days. CALCULATING THE PQOL-12 SCORE WITHIN THE KMPI To be consistent with the desire for the KMPI to be a simple and easily used tool within clinical practice, the calculation of the PQOL-12 score for use within the KMPI differs from how the PQOL-12 score is reported above. Whereas the PQOL-12 score above ranges from 0 (best) to 10 (worst) and is calculated by taking the mean of the item scores, the scoring for the PQOL-12 within the KMPI does not involve calculating mean item score but rather uses a simple sum of the item scores for a score that ranges from 0 (best) to 120 (worst). As the burden of psoriasis on a patient’s health-related and psoriasisspecific quality-of-life is determined by a range of variables unique to each patient’s disease symptoms and life-circumstances, a comprehensive and practical approach was employed to determine a PQOL-12 score criterion

Koo–Menter Psoriasis Instrument

27

for use within Part 3 of the KMPI. Qualitative review of the data from Study 1 and Study 2 along with quantitative analyses (i.e., exploratory cluster analysis) was conducted to identify if there was a natural ‘‘cut-point’’ between patients with mild and moderate psoriasis that was relatively stable over the various patient- and physician-rated severity measures. In addition, we sought to balance this with a cut-off point where a therapeutic intervention might be expected to have an impact on psoriasis-specific quality-of-life, while also accounting for the minimum important difference on the PQOL-12, which is approximately 1 to 2 points. Analysis results indicated that such a cut-off point might be as low as a score of 25 using the scoring method for the PQOL-12 within the KMPI, however, clinical opinion suggested the use of a more conservative 50 points for the final instrument. Further research is needed to better understand the minimum point where treatment might positively impact psoriasis patients based on their PQOL-12 score.

DISCUSSION ON KMPI The KMPI provides a quick and easy way to identify and document patients with psoriasis who require systemic therapy. The KMPI is short enough to be completed during a routine visit to a dermatologist. It takes approximately five minutes for the patient to complete the front page of the instrument while waiting in the reception area or the examination room prior to being seen by the physician. Similarly, the physician assessment takes approximately five to seven minutes to complete and the resulting instrument can become part of the patient’s medical record for reference at subsequent patient visits. The KMPI is unique in providing a complete evaluation of the patient’s disease status-incorporating assessments of psoriasis-specific quality-of-life with a validated questionnaire (PQOL-12), psoriasis severity and psoriatic joint disease. The KMPI alerts the physician and patient of the need to assess health-related quality-of-life and joint-related symptoms in the clinical evaluation of psoriasis and determines the suitability (or otherwise) for systemic therapy in individual patients. The KMPI has the potential to improve physician–patient communication by involving the patient in characterizing their disease and its impact on their lives.

CONCLUSION The KMPI is a practical assessment tool that dermatologists can quickly and easily use in their daily practice to help guide them in identifying

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patients with psoriasis who may be candidates for systemic therapy, as well as to justify these decisions to third-party payers. REFERENCES 1. Krueger G, Koo J, Lebwohl M, et al. The impact of psoriasis on quality of life. Results of a 1998 National Psoriasis Foundation patient-membership survey. Arch Dermatol 2001; 137:280–284. 2. Krueger GG, Feldman SR, Camisa C, et al. Two considerations for patients with psoriasis and their conicians: What defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis? J Am Acad Dermatol 2000; 43:281–285. 3. Koo J, Kozma CM, Reinke K. The development of a disease-specific questionnaire to assess the quality of life for psoriasis patients: an analysis of the reliability, validity, and responsiveness of the psoriasis quality of life questionnaire. Dermatologie Psychosomatik 2002; 3:171–179. 4. Feldman S, Koo J, Menter A, Bagel J. Decision points for the initiation of systemic treatment for psoriasis. JAAD 2005; 53(1):101–107. 5. Koo J. Population-based epidemiologic study of psoriasis with emphasis on quality of life assessment. Dermatol Clin 1996; 14:485–496. 6. Koo JY, Martin D. Investigator-masked comparison of tazarotene gel q.d. plus mometasone furoate cream q.d. vs. mometasone furoate cream b.i.d. in the treatment of plaque psoriasis. Int J Dermatol 2001; 40:210–212. 7. Koo J, Menter A, Lebwohl M, et al. The relationship between quality of life and disease severity: results from a large cohort of mild, moderate, and severe psoriasis patients [abstr]. Br J Dermatol 2002; 147:1078. 8. Koo J, Kozma CM, Menter A, et al. Development of a disease-specific quality of life questionnaire: the 12-item Psoriasis Quality of Life Questionnaire (PQOL-12). 61st Annual Meeting of the American Academy of Dermatology, 2003. 9. Ware JE, Harris, Gandek WJ, Rogers BW, Reese PR. MAP-R for Windows: multitrait/multi-tem scale analysis software user’s manual, Boston, MA, 1997. 10. Juniper EF, Guyatt GH, Willan A, Griffith LE. Determining a minimal important change in a disease-specific quality of life questionnaire. J Clin Epidemiol 1994; 47(1):81–87.

4 General Guidelines for Administration of Topical Agents in the Treatment of Mild-to-Moderate Psoriasis Jashin J. Wu and Gerald D. Weinstein Department of Dermatology, University of California, Irvine, California, U.S.A.

Psoriasis is a chronic inflammatory disorder of the skin that affects 2% of the world (1). It is one of the more commonly seen and treated diseases for the general dermatologist, amounting to approximately 2.3% to 10% of the office practice (2,3). In a survey of dermatologists who belong to the American Academy of Dermatology, approximately 70% of psoriasis patients were treated with topical therapies and 30% with phototherapy/ systemic therapy (4). In another report, it is estimated that 75% of psoriasis patients have mild-to-moderate disease [as measured by