INTRODUCTION
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.
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
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, placeboâ€controlled, randomized phase IIa trial, the safety and efficacy of twice daily (BID) 0.5% tapinarof cream
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, placeboâ€controlled, randomized phase IIa trial, the safety and efficacy of twice daily (BID) 0.5% tapinarof cream
