Topical Agents Currently in Phase II or Phase III Trials for Atopic Dermatitis
October 2020 | Volume 19 | Issue 10 | Original Article | 956 | Copyright © October 2020
Published online September 18, 2020
Shelley K. Uppal BSa, Vipawee S. Chat BAb, Donovan G. Kearns BSc, Jashin J. Wu MDd
aAlbany Medical College, Albany, NY bMedical College of Georgia at Augusta University, Augusta, GA cLoma Linda School of Medicine, Loma Linda, CA dDermatology Research and Education Foundation, Irvine, CA
Mild to moderate atopic dermatitis (AD) occurs frequently in children and adults and is usually managed through the use of pharmacologic treatments, such as topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs), and good skin care practices. As chronic TCS or TCI can lead to the development of adverse effects, there is a need for safe, alternative treatments for patients with resistant AD. A systemic literature review was performed to examine the safety and efficacy of topical agents currently in phase II and phase III clinical trials for AD. Our team searched the databases, PubMed, Google Scholar, and ClinicalTrials.gov, on March 2020 for studies pertaining to the use of topical agents in AD. Key words included each drug (tapinarof, crisaborole, ARQ-151 cream, ruxolitinib) or “topical agents” combined with “atopic dermatitis.” Articles published within the last 5 years were included as references. References within retrieved articles were also reviewed to identify potentially missed studies. A total of 24 articles were included in this review. Tapinarof, crisaborole, and ruxolitinib lead to statistically significant improvements in multiple disease severity scores. ARQ-151 cream achieved statistical significance in secondary endpoints, including vIGA-AD and EASI-75, but not in the primary endpoint of the study. All topical agents were well-tolerated by study participants. The findings demonstrate that tapinarof, crisaborole, ARQ-151 cream, and ruxolitinib are safe, effective treatment options for patients with mild to moderate AD. J Drugs Dermatol
. 2020;19(10):956-959. doi:10.36849/JDD.2020.5214
Atopic dermatitis (AD) is a pruritic, inflammatory skin disease that affects approximately 5–30% of children and 2–10% of adults.1-3 The pathogenesis of AD involves a complex interplay of skin barrier defects, dysregulation of the innate immune response, defects in the adaptive immune response, Th2 immune polarization, and an altered skin microbiome.2 In most cases, AD is successfully managed through elimination of exacerbating factors, good skin care practices, and topical therapies.3,4 Long term use of topical corticosteroids (TCS), which are considered to be first-line treatment for AD flares, carries the risks of skin atrophy, local skin reactions (telangiectasia, striae and purpura, focal hypertrichosis, hypopigmentation, perioral dermatitis), percutaneous absorption, and rebound flares with discontinued use.3-5 Topical calcineurin inhibitors (TCIs), the second-line treatment for AD, comes with a FDA Black Box Warning based on the theoretical risk of lymphoma or cutaneous cancer from systemic calcineurin inhibitors in animal studies and transplant patients.4,5 Therefore, there is a need for alternative safe, long-term treatments for patients with resistant AD in whom chronic TCS or TCI use may lead to development of adverse effects.
In recent years, a better understanding of the underlying pathologic mechanisms in AD has led to the development of novel, targeted therapies. In 2020, the FDA approved the use of EucrisaTM (crisaborole) for topical treatment of mild-to-moderate AD in patients 3 months of age and older. Novel topical therapies— tapinarof, ARQ-151 cream, and ruxolitinib—are promising treatments options currently in investigation for AD. The purpose of this review is to discuss these four agents in depth and the current evidence behind their use.
MATERIALS AND METHODS
Tapinarof (GSK2894512 cream, WBI-1001, or BenvitimodTM) is a therapeutic aryl hydrocarbon receptor (AHr) modulating agent under investigation for the treatment of AD and plaque psoriasis.6 Tapinarof’s pharmacologic effect is primarily mediated through agonism of AHr, a cytosolic ligand-activated receptor that affects Th2 cytokine and epidermal barrier gene expression in human keratinocytes.7 AHr regulates innate and adaptive immune responses in the skin and is critical in the development and maintenance of the skin barriers, especially in response to noxious stimuli.7 In addition to anti-inflammatory properties, tapinarof also exhibits antioxidant properties through the activation of nuclear (erythroid-derived 2)-like 2 pathway.7,8
In a double blind, placebo‐controlled, randomized phase IIa trial, the safety and efficacy of twice daily (BID) 0.5% tapinarof cream