Topical Agents for the Treatment of Atopic Dermatitis

January 2020 | Volume 19 | Issue 1 | Editorials | 50 | Copyright © January 2020


Published online December 5, 2019

Lawrence F. Eichenfield , Thomas Luger , Kim Papp , Jonathan I. Silverberg , Debra Sierka , Chuanbo Zang , Anna M. Tallman , Michael A. Zielinski , William C. Ports

aUniversity of California, San Diego, San Diego, CA bRady Children’s Hospital-San Diego, San Diego, CA cWestphalian Wilhelms-University Münster, Münster, Germany dK Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada eThe George Washington University School of Medicine and Health Sciences, Washington, DC fPfizer Inc., Collegeville, PA gPfizer Inc., New York, NY hPfizer Inc., Groton, CT *At the time of this research

Abstract
Approval of the new topical phosphodiesterase 4 inhibitor crisaborole ointment, 2%, to treat mild-to-moderate atopic dermatitis (AD) warrants careful consideration of available efficacy and safety data for topical therapies to contribute to a better understanding of the role of crisaborole in the treatment of mild-to-moderate AD. A literature review was conducted to identify results of randomized, blinded, vehicle-controlled trials of topical agents for the treatment of AD published from January 1, 1997 to April 30, 2018. This review summarizes the efficacy and safety data of topical therapies including corticosteroids, calcineurin inhibitors, and crisaborole and it shows that comparison among available agents is difficult because of differing methodologies used across clinical trials and that there is considerable variability in safety reporting among AD trials. Published clinical studies for crisaborole demonstrate its efficacy and manageable safety profile.

J Drugs Dermatol. 2020;19(1):50-64. doi:10.36849/JDD.2020.4508

INTRODUCTION

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that follows a chronic and relapsing course.1 Essential features include pruritus and eczematous lesions that present with a typical morphology and age-associated distribution.2,3 Up to 90% of children with AD have mild or moderate disease.4 Common signs and symptoms include pruritus, erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and lichenification, which vary by age and chronicity of lesions.2 Because of the chronicity, intense symptom burden, and visible nature of the disease, patients with AD frequently have reduced quality of life (QoL) and psychological comorbidities, including depression and anxiety.5 Pruritus is responsible for a significant portion of this burden, which includes the associated impact on sleep quality.2,6

According to the American Academy of Dermatology (2014) and joint guidelines of the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology (2013), topical therapies remain standard treatment for AD and provide efficacy while minimizing the potential for systemic adverse events (AEs).7,8 Basic skin care, moisturizers, and trigger avoidance are recommended as initial treatment and are integral to AD therapy, aiming to treat and prevent xerosis, reduce transepidermal water loss (TEWL), reduce signs of AD, and prevent flares.7,8 When the AD is not sufficiently controlled with nonpharmacologic approaches, topical corticosteroids (TCSs) are recommended.7,8 TCSs have been the mainstay of anti-inflammatory therapy for AD for decades and can be used reactively to treat established lesions and proactively to prevent relapse.7 However, safety concerns regarding local and systemic AEs can result in treatment hesitancy in caregivers and patients.7,9 Therefore, appropriate selection of TCS potency, correct application (including duration and location of treatment), and patient education are important.7,8 Topical calcineurin inhibitors (TCIs) are immunosuppressant agents that are recommended as second-line treatment in areas where skin atrophy is a concern (eg, face, eyelids, skin folds), for steroid-nonresponsive AD, when steroids are not advisable, or when a TCS treatment holiday is necessary.7,8 Transient localized burning and itching can occur with TCIs, which can limit their use in some patients.7,8

Crisaborole ointment is a nonsteroidal, phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild-to-moderate AD.