Topical Therapy for Atopic Dermatitis: New and Investigational Agents
Recently a new class of topical medications for mild to moderate atopic dermatitis has been introduced with US Food and Drug Administration (FDA) approval of the first new prescription medication for this condition in more than a decade. Crisaborole, the newly approved medication, has relieved pruritus in more than one-third of patients within as little as 48 hours. It also has demonstrated efficacy in patients with skin of color. Topical therapies representing other new approaches to atopic dermatitis, with novel mechanisms of action, have shown promise in clinical development.
Semin Cutan Med Surg 36(supp4):S99-S102
© 2017 published by Frontline Medical Communications
Atopic dermatitis; crisaborole; INCB018424; MM36; pruritus; skin of color; tapinarof
Atopic dermatitis is a chronic relapsing condition that can have a substantial impact on quality of life.1,2 The goal of therapy is to treat to no or minimal disease and symptoms.
Most patients can obtain safe and effective relief with nonpharmacologic and prescription topical treatment.3 Bathing, moisturizing, preventing skin infections, and topical corticosteroids and topical calcineurin inhibitors remain important components of therapy. In those cases which such measures do not provide adequate control over the disease, new and investigational therapies may offer additional options.
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/atopicdermsupl2017.
Inquiries about CME accreditation may be directed to the University of Louisville Office of Continuing Medical Education & Professional Development (CME & PD) at [email protected] or (502) 852-5329.
Lawrence F. Eichenfield, MD
Linda F. Stein Gold, MD
Wynnis L. Tom, MD
Physicians: This activity has been planned and implemented in accor- dance with the requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the University of Louisville and Global Academy for Medical Education, LLC. The University of Louisville is accredited by the ACCME to provide continuing medical education for physicians.
The University of Louisville Office of Continuing Medical Education & Professional Development designates this enduring material for a maximum of 1.75 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Nurses: Postgraduate Institute for Medicine is accredited with distinction as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.This educational activity for 1.6 contact hour is provided by the Postgraduate Institute for Medicine. Designated for 0.8 contact hours of pharmacotherapy credit for Advance Practice Nurses.
Recent research into the pathophysiology of atopic dermatitis has yielded two new treatments—the first ones to receive US Food and Drug Administration (FDA) approval for management of this condition in more than a decade. Both new therapies offer novel mechanisms of action. Crisaborole, a topical medi- cation that inhibits the phosphodiesterase-4 (PDE-4) enzyme, is approved for the treatment of mild to moderate disease in adults and children as young as 2 years old. Dupilumab, the first biologic therapy approved for use in atopic dermatitis, inhibits interleukin (IL)-4 and IL-13. It is indicated for the treatment of moderate to severe disease in adults whose disease is inadequately controlled with topical prescription therapies, or when those therapies are inadvisable.
Awareness of the substantial impact atopic dermatitis can have on quality of life can facilitate patient-clinician conversations about treatment goals. Such discussions may influence shared decision-making about therapeutic choices.
Therapeutic patient education has been applied to a variety of conditions and is now being studied in atopic dermatitis.
Food allergy and infection represent common comorbidities in patients with atopic dermatitis. New information about the benefit of the early introduction of peanuts to the diet has surfaced in recent years. Alterations in the skin microbiome may underlie the association of colonization and infection in atopic dermatitis. Preliminary research attempts to deploy the atopic patient’s “good” bacteria to reduce Staphylococcus aureus colonization.
Brief, expert reviews of the literature in these areas can help busy providers stay current in a rapidly evolving field, and can facilitate the translation of research into clinical practice to improve outcomes.
By reading and studying this supplement, participants should be better able to:
- Demonstrate an understanding of how atopic dermatitis can affect patient sleep, quality of life, daily activities, risk of comorbidities, and health care utilization/cost
- Explain the mechanism of action and clinical trials data supporting recently approved treatments for atopic dermatitis
- Discuss investigation therapies for atopic dermatitis
- Apply recent recommendations for evaluation of candidates for systemic treatment of atopic dermatitis
- Explain the benefit of providing patients with a written action plan
- Analyze the relationships of food allergy and infection to atopic dermatitis.
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: Eli Lilly and Company, Genentech, Inc., Otsuka America Pharmaceutical, Inc./Medimetriks Pharmaceuticals, Inc., Pfizer Inc., Sanofi Genzyme/Regeneron Pharmaceuticals, TopMD, Valeant. Investigator: Sanofi Genzyme/Regeneron.
Linda F. Stein Gold, MD, Consultant: Pfizer. Grant/Research: GlaxoSmithKline and Pfizer. Data Monitoring Committee: Otsuka.
Wynnis L. Tom, MD, Consultant: Pfizer. Grant/Research: Pfizer, Celgene Corporation, Pfizer, and Regeneron.
University of Louisville CME & PD Advisory Board and Staff Disclosures:
The CME & PD Advisory Board and Staff have nothing to disclose.
CME/CE Reviewers: University of Louisville Cindy England Owen, MD, has nothing to disclose. The Postgraduate Institute of Medicine 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: Eileen McCaffrey, MA; Tristan M. Nelsen, MNM, CMP, HMCC; Sylvia H. Reitman, MBA, DipEd; and Ron Schaumburg have nothing to disclose.
Off-Label/Investigational Use Disclosure
This CME/CE activity discusses the off-label use of certain approved medica- tions as well as data from clinical trials on investigational agents. Any such material is identified within the text of the articles.
This continuing medical education (CME/CE) supplement was developed from a satellite symposium held at the Skin Disease Education Foundation’s 18th Annual Las Vegas Dermatology Seminar, November 3, 2017, in Las Vegas, Nevada. The Guest Editors acknowledge the editorial assistance of Global Academy for Medical Education and Eileen McCaffrey, MA, 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.
Eichenfield LF, Tom WL, Berger TG, 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(1):116-132.
Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: an analysis using the National Health and Wellness Survey. J Am Acad Dermatol. 2017;77(2):274-279.e273.
Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327-349.
Cabanillas B, Brehler AC, Novak N. Atopic dermatitis phenotypes and the need for personalized medicine. Curr Opin Allergy Clin Immunol. 2017;17(4):309-315.
Levy J, Zhou DM, Zippin JH. Cyclic adenosine monophosphate signaling in inflammatory skin disease. J Clin Exp Dermatol Res. 2016;7(1):326.
Hanifin JM, Chan SC. Monocyte phosphodiesterase abnormalities and dysregu- lation of lymphocyte function in atopic dermatitis. J Invest Dermatol. 1995;105 (1 Suppl):84s-88s.
Hanifin JM, Chan SC, Cheng JB, et al. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. J Invest Dermatol. 1996;107(1):51-56.
Akama T, Baker SJ, Zhang YK, et al. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett. 2009;19(8):2129-2132.
Jarnagin K, Chanda S, Coronado D, et al. Crisaborole topical ointment, 2%: a nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 inhibitor in clinical development for the treatment of atopic dermatitis. J Drugs Dermatol. 2016;15(4):390-396.
Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole oint- ment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503.e494.
Paller AS, Yosipovitch G, Tom W, et al. Crisaborole ointment improves global atopic dermatitis severity and provides early relief in pruritus: pooled results from two phase 3 clinical trials. American Academy of Pediatrics National Conference and Exhibition; September 16-19, 2017; Chicago, IL.
von Kobyletzki LB, Thomas KS, Schmitt J, et al. What factors are important to patients when assessing treatment response: an international cross-sectional survey. Acta Derm Venereol. 2017;97(1):86-90.
Callender VD, Alexis AF, Stein Gold LF, et al. Efficacy and safety of crisaborole ointment, 2%, for treatment of mild to moderate atopic dermatitis across racial and ethnic groups. European Poster presentation at: Academy of Dermatology and Venereology (EADV) Congress; Sept. 13-17, 2017, 2017; Geneva, Switzerland. Poster P0270.
Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131(1):67-73.
Eichenfield LF, Call RS, Forsha DW, et al. Long-term safety of crisaborole oint- ment 2% in children and adults with mild to moderate atopic dermatitis. J Am Acad Dermatol. 2017;77(4):641-649.e645.
Hanifin JM, Ellis CN, Frieden IJ, et al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): a phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016;75(2):297-305.
Eichenfield LF, Ellis CN, Haruta J, Rosenberg N, Roth S, Stein Gold LF. MM36 review: selective inhibition of PDE4 subtype B is effective in the topical treatment of atopic dermatitis. 45th European Society for Dermatological Research; September 9-12, 2015, 2015; Rotterdam, The Netherlands.
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(4):495-504.
Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof Is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 2017;137(10):2110-2119.
Bissonnette R, Chen G, Bolduc C, et al. Efficacy and safety of topical WBI-1001 in the treatment of atopic dermatitis: results from a phase 2A, randomized, placebocontrolled clinical trial. Arch Dermatol. 2010;146(4):446-449.
Maeda-Chubachi T, Johnson LV, Bullman J, Collingwood T, Bissonnette R. Tapinarof cream for atopic dermatitis: pharmacokinetics, systemic exposure, and preliminary efficacy/safety results. J Am Acad Dermatol. 2017;76(6 Suppl 1): AB247.
Punwani N, Burn T, Scherle P, et al. Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor. Br J Dermatol. 2015;173(4):989-997.
*Director of Dermatology Research, Henry Ford Health System, Detroit, Michigan
† Professor of Dermatology and Pediatrics, Vice Chair, Department of Dermatology, Chief, Pediatric and Adolescent Dermatology, University of California, San Diego School of Medicine and Rady
Children’s Hospital, San Diego, University of 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 Pfizer Inc. The authors have received an honorarium for their participation in this activity. They acknowledge the editorial assistance of Eileen McCaffrey, MA, medical writer, and Global Academy for Medical Education in the development of this continuing medical education journal article.
Linda F. Stein Gold, MD, Consultant: Pfizer. Grant/Research: GlaxoSmithKline and Pfizer. Data Monitoring Committee: Otsuka America Pharmaceutical, Inc.
Lawrence F. Eichenfield, MD, Advisory Board/Speaker: Valeant Pharmaceuticals North America LLC. Consultant: Eli Lilly and Company, Genentech, Inc., Otsuka/Medimetriks Pharmaceuticals, Inc., Pfizer, 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 protected]