Systemic Therapy of Atopic Dermatitis: Welcome to the Revolution
Until recently, systemic therapy of atopic dermatitis was limited to off-label use of immunomodulators, which can pose significant safety concerns, and treatment with systemic corticosteroids, not recommended in the most recent guidelines.The introduction of dupilumab in 2017 marked a major advance in systemic therapy for atopic dermatitis. It has demonstrated long-term efficacy in adults with moderate to severe disease, and is being studied in children. Several other biologic agents and “small molecules” with varying mechanisms of action are in phase 2 or 3 development. Semin Cutan Med Surg 36(supp4):S103-S105
© 2017 published by Frontline Medical Communications
Atopic dermatitis; dupilumab; fezakinumab; JAK inhibitors; lebrikizumab; nemolizumab; systemic therapy; tralokinumab
Most patients with atopic dermatitis may be adequately managed with nonpharmacologic measures (eg, emollients), topical anti-inflammatory therapies, environmental modification (eg, avoiding triggers), and for some, phototherapy. However, for patients who do not respond to treatment, available options have been both limited and problematic. Immunosuppressive agents have been used—azathioprine, cyclosporine, methotrexate, and mycophenolate—but are unapproved in the United States for atopic dermatitis and are associated with serious adverse effects. Although systemic corticosteroids are prescribed clinically, guidelines advise against their use for most patients, again due to their potential adverse effects.1
Recognizing that there are many individuals with atopic dermatitis who are inadequately controlled with topical medications and appropriate skin and adjuvant care, and the tremendous impact of atopic dermatitis on the lives of affected individuals, there is a great clinical need for systemic therapies with efficacy and superior safety profiles. The introduction of the biologic agent dupilumab in early 2017 represented a milestone for patients who need treatment beyond conventional and topical interventions. At least seven other biologic therapies or small molecular agents are in phase 2 or 3 study for atopic dermatitis at this writing.
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.
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.
Simpson EL, Bruin-Weller M, Flohr C, et al. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol. 2017;77(4):623-633.
Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 2017.
Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double- blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287-2303.
Cork MJ, Thaçi D, DiCioccio AT, et al. Pharmacokinetics, safety, and efficacy of dupilumab in a pediatric population with moderate-to-severe atopic dermatitis: Results from an open-label phase 2a trial. Presented at the American Academy of Dermatology Meeting in Orlando, FL, USA; March 3-7, 2017.
Eichenfield LF, Flohr C, Simpson E, et al. Lebrikizumab improves patient-reported outcomes (PROs) in a phase 2 study in patients with atopic dermatitis. Presented at the annual meeting of the American Academy of Dermatology, Orlando, Florida, USA, March 3-7, 2017.
Wollenberg A, Howell MD, Guttman-Yassky E, et al. A phase 2b dose-ranging efficacy and safety study of tralokinumab in adult patients with moderate to severe atopic dermatitis (AD). Presented at the American Academy of Dermatology Meeting in Orlando, FL, USA; March 3-7, 2017.
Ruzicka T, Hanifin JM, Furue M, et al. Anti–interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826-835.
Guttman-Yassky E, Khattri S, Brunner PM, et al. A pathogenic role for Th22/ IL-22 in atopic dermatitis is established by a placebo-controlled trial with an anti IL-22/ILV-094 mAb (abstract 313). J Invest Dermatol. 2017;137(5):S53.
*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
† Director of Dermatology Research, Henry Ford Health System, Detroit, Michigan
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.
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, 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.
Address reprint requests to: Lawrence F. Eichenfield, MD, Rady Children’s Hospital, 8010 Frost Street, Suite 602, San Diego, CA 92123; [email protected]