Nonpharmacologic Strategies and Topical Agents for Treating Atopic Dermatitis: An Update
Eichenfield and colleagues5 studied the efficacy and safety of pimecrolimus cream 1% vs vehicle in two 6-week, randomized, multicenter studies involving 403 children and adolescents with mild (30%), moderate (60%), and severe (9%) AD. All patients had BSA involvement of at least 5%. As early as day 8, a statistically significant improvement was seen on the investigator’s global score of clear or almost clear in the active-treatment group vs vehicle (P≤0.05).
In a 12-week randomized, double-blind, vehicle-controlled study, Paller and colleagues6 evaluated the safety and efficacy of tacrolimus ointment 0.03% and 0.1% in pediatric patients with moderate to severe AD. A total of 352 children between 2 and 15 years of age (mean age, 6.1 years) were enrolled; 61.5% had severe AD at baseline; 83.5% of patients had involvement of the head/face and/or neck. At week 12, significantly more patients in the tacrolimus treatment groups had clinical improvement of at least 90% than did patients in the vehicle group (P≤0.001). The authors noted that in the active-treatment groups, improvements in AD signs and symptoms, BSA affected, and patients’ assessment of pruritus were seen early in the study and were maintained through week 12. Several adverse events occurred more frequently in the higher-concentration tacrolimus treatment groups than in the vehicle group: a sensation of burning, pruritus, varicella, and blisters (the incidence of varicella and blisters was <5%). (Note that only the 0.03% concentration is approved by the US Food and Drug Administration for use in patients <15 years of age.)
Gollnick and colleagues7 studied pimecrolimus cream 1% in the long-term management of AD in adults, with the goal of determining the effectiveness of this agent in preventing the progression of flares. The 543 enrolled patients were at least 18 years of age and had mild or moderate AD. Their AD was clear or almost clear before they were randomized to receive pimecrolimus cream (n=277) or vehicle only (n=266) in this 26-week study. Twice-daily applications of the study medication (either pimecrolimus or vehicle) were started as soon as a patient had any sign or symptom of a relapse. If the disease worsened, patients were permitted to add a moderately potent topical corticosteroid after the study medication had been used for at least 3 days. The primary endpoint was the number of days elapsed before corticosteroid treatment was needed to control a flare. The investigators reported that the mean number of corticosteroid-free days was significantly higher in the active-treatment group (152 days) than in the vehicle group (138.7 days) (P<0.001); moreover, the mean number of flares requiring corticosteroid treatment was lower in the pimecrolimus group (P=0.0014).
The guidelines for topical treatment of AD8 note that TCIs are valuable as corticosteroid-sparing agents; TCIs should be prescribed for the treatment of actively affected areas. If necessary, a topical corticosteroid can be used with a TCI to bring an AD flare under control.
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Participants should read the activity information, review the activity in its entirety, and complete the online post-test and evaluation. Upon completing this activity as designed and achieving a passing score on the post-test, 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 out at that time. The online post-test and evaluation can be accessed at http://tinyurl.com/meetingthechallengeofatopic. Inquiries about CME accreditation may be directed to the University of Louisville Office of Continuing Medical Education & Professional Development (CME & PD) at email@example.com or (502) 852-5329.
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The diagnosis of atopic dermatitis can be challenging because the type and appearance of skin lesions can vary and some common cutaneous conditions—such as seborrheic dermatitis (“cradle cap”) in infants—may coexist. In most cases, attention to characteristic features of AD leads to the correct diagnosis. Awareness of clinical circumstances that should lead to consideration of some rare conditions in the differential diagnosis also is important.
Recently published studies that have furthered the understanding of the role of filaggrin, filaggrin gene mutations, and transepidermal water loss have demonstrated that daily, full-body emollient applications, beginning at birth, may prevent the expression of AD in susceptible children. For all patients with AD, the use of adequate skin hydration combined with the prompt application of ointment or cream moisturizers (“soak and seal”) remains the cornerstone of AD therapy.
Recent advances in understanding the complex pathophysiology of AD have led to the development of new and emerging topical and systemic medications that may effectively manage the signs and symptoms of AD in patients who do not respond adequately to standard treatment regimens. These include the topical phosphodiesterase-4 inhibitor crisaborole, recently approved for use in AD by the US Food and Drug Administration (FDA), and the subcutaneously administered interleukin-4 receptor α subunit inhibitor dupilumab, for which phase III pivotal study data are now available.
Clinicians must remain up-to-date on the findings from clinical studies on the diagnosis and management of AD, as well as the benefits and risks of all treatment options available, to make the appropriate choices for management of their individual patients.
By reading and studying this supplement, participants should be better able to:
- Discuss the features of AD that should allow a clinical diagnosis of the condition in most patients, and list the factors in children and adults that should lead to the consideration of alternative diagnoses or identification of comorbid conditions.
- Explain how the current understanding of the role of the epidermal skin barrier and transepidermal water loss should affect—and continue to improve— the day-to-day care of patients with AD.
- More effectively individualize patient treatment strategies by considering the full range of current and emerging therapeutic options.
- Consider the evidence-based recommendations in the current guidelines for the diagnosis and treatment of AD published by the American Academy of Dermatology.
- Describe the rationales and mechanisms of action of the new and emerging therapies for AD, particularly the recently approved topical agent crisaborole and the systemic medication dupilumab (phase III study results under FDA review at the time of publication of this supplement).
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.
Lawrence F. Eichenfield, MD, Advisory Board/Speaker: Valeant Pharmaceuticals North America LLC. Consultant: Anacor Pharmaceuticals, Inc./Pfizer Inc., Eli Lilly and Company, Genentech, Inc., Otsuka America Pharmaceutical, Inc./Medimetriks Pharmaceuticals, Inc., Sanofi Genzyme/Regeneron Pharmaceuticals, TopMD, Valeant. Investigator: Sanofi Genzyme/Regeneron.
Linda F. Stein Gold, MD, Consultant: Anacor. Grant/Research: Anacor, GlaxoSmithKline. Data Monitoring Committee: Otsuka.
Staff and Advisory Board Disclosures: The CME & PD staff pediatricians, family practitioners, and Advisory Board have nothing to disclose.
CME/CE Reviewers: Cindy England Owen, MD, Assistant Professor, Division of Dermatology, University of Louisville School of Medicine, has no relevant financial relationships to disclose. The PIM planners and managers, Trace Hutchison, PharmD; Samantha Mattiucci, PharmD, CHCP; Judi Smelker- Mitchek, MBA, MSN, RN; and Jan Schultz, MSN, RN, CHCP, have nothing to disclose.
Global Academy for Medical Education Staff: Sylvia H. Reitman, MBA, DipEd; Jenny Campano; Tristan Nelsen, MNM, CMP, HMCC; and Joanne Still have no relevant financial relationships to disclose.
Off-Label/Investigational Use Disclosure
This CME/CE activity discusses the off-label use of certain approved medications as well as data from clinical trials on investigational agents. Any such material is identified within the text of the articles.
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Copyright © 2017 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, Global Education Group, and Frontline Medical Communications 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.
1. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009;123:e808-e814.
2. Shi VY, Foolad N, Omelas JN, et al. Comparing the effect of bleach and water baths on skin barrier function in atopic dermatitis: A split-body randomized controlled trial. Br J Dermatol. 2016;175:212-214.
3. Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics. 2008;122:812-824.
4. Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol. 2002;147:528-537.
5. Eichenfield LF, Lucky AW, Boguniewicz M, et al. Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Acad Dermatol. 2002;46:495-504.
6. Paller A, Eichenfield LF, Leung DY, Stewart D, Appell M. A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol. 2001;44(suppl):S47-S57.
7. Gollnick H, Kaufmann R, Stough D, et al. Pimecrolimus cream 1% in the longterm management of adult atopic dermatitis: Prevention of flare progression. A randomized controlled trial. Br J Dermatol. 2008;158:1083-1093.
8. Eichenfield LF, Tom WL, Berger, et al. Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116-132.
9. Luger T, Boguniewicz M, Carr W, et al. Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants. Pediatr Allergy Immunol. 2015;26:306-315.
This continuing medical education (CME/CE) supplement was developed from a satellite symposium held at the Skin Disease Education Foundation’s 17th Annual Las Vegas Dermatology Seminar, November 11, 2016, in Las Vegas, Nevada. 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 supporter, Global Academy for Medical Education, the University of Louisville, Postgraduate Institute for Medicine, or the Publisher.
* Director of Dermatology Research, Henry Ford Health System, Detroit, Michigan
† Chief, Pediatric and Adolescent Dermatology, Professor of Dermatology and Pediatrics, Rady Children’s Hospital, University of California, San Diego School of Medicine, San Diego, California
Publication of this CME/CE article was jointly provided by University of Louisville, Postgraduate Institute for Medicine, and Global Academy for Medical Education, LLC, and is supported by an educational grant from Anacor Pharmaceuticals, Inc. The authors 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.
Linda F. Stein Gold, MD, Consultant: Anacor. Grant/Research: Anacor, GlaxoSmithKline. Data Monitoring Committee: Otsuka America Pharmaceutical, Inc.
Lawrence F. Eichenfield, MD, Advisory Board/Speaker: Valeant Pharmaceuticals North America LLC. Consultant: Anacor/Pfizer Inc., Eli Lilly and Company, Genentech, Inc., Otsuka/Medimetriks Pharmaceuticals, Inc., Sanofi Genzyme/Regeneron Pharmaceuticals, TopMD, Valeant. Investigator: Sanofi Genzyme/Regeneron.
Address reprint requests to: Linda F. Stein Gold, MD, 2360 Heronwood Drive, Bloomfield Hills, MI 48302; email@example.com
© 2017 Frontline Medical Communications 1085-5629/13/$-see front matter doi:10.12788/j.sder.2017.011