Tapinarof, a Novel, First-in-Class, Topical Therapeutic Aryl Hydrocarbon Receptor Agonist for the Management of Psoriasis
August 2023 | Volume 22 | Issue 8 | 779 | Copyright © August 2023
Published online July 10, 2023
Margaret Bobonich DNP FNP-C DCNP FAANPa, Joe Gorelick MSN FNP-Cb, Lakshi Aldredge MSN ANP-BC DCNP FAANPc, Matthew J. Bruno PA-Cd, Douglas DiRuggiero DMSc MHS PA-Ce, George Martin MDf, Anna M. Tallman PharmDg, Linda Stein Gold MDh
aDepartment of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH
bDepartment of Dermatology, California Skin Institute, San Jose, CA
cDermatology Service, Operative Care Division, VA Portland Healthcare System, Portland, OR
dClinical Development, Dermatology & Skin Cancer Surgery Center, Allen, TX
eDermatology, Skin Cancer & Cosmetic Dermatology Center, Rome, GA
fDermatology, George Martin Dermatology Associates, Kihei, HI
gMedical Affairs, Dermavant Sciences, Inc., Morrisville, NC
hDepartment of Dermatology, Henry Ford Health System, Detroit, MI
Abstract
Topical treatments remain the foundation of psoriasis management. Tapinarof (VTAMA®; Dermavant Sciences, Inc.) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor (AhR) agonist approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults and is under investigation for the treatment of psoriasis in children, and atopic dermatitis in adults and children down to 2 years old. Here, we review the mechanism of action of tapinarof and the PSOARING phase 3 trial program in mild to severe psoriasis. AhR is a ligand-dependent transcription factor involved in maintaining skin homeostasis. Tapinarof specifically binds to AhR to decrease proinflammatory cytokines, decrease oxidative stress, and promote skin barrier normalization. In two identical, randomized, 12-week pivotal phase 3 trials, PSOARING 1 and 2, tapinarof cream 1% once daily (QD) demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild to severe psoriasis. In the PSOARING 3 long-term extension trial of repeated, intermittent tapinarof cream in eligible patients completing the pivotal trials, a high rate of complete disease clearance (40.9%) and a remittive effect of approximately 4 months off therapy were demonstrated over 52 weeks, with no tachyphylaxis. The most common adverse event, folliculitis, was mostly mild or moderate and resulted in a low trial discontinuation rate in PSOARING 1 and 2 (≤1.8%). Tapinarof cream 1% QD provides a novel, non-steroidal, topical treatment option for patients with psoriasis and is highly effective and well tolerated with long-term use including when applied to sensitive and intertriginous skin.
Bobonich M, Gorelick J, Aldredge L, et al. Tapinarof, a novel, first-in-class, topical therapeutic aryl hydrocarbon receptor agonist for the management of psoriasis. J Drugs Dermatol. 2023;22(8):779-784. doi:10.36849/JDD.7317
INTRODUCTION
Current Treatments and Unmet Needs in Psoriasis
Psoriasis is a chronic, immune-mediated skin disease that affects approximately 8 million adults in the Unite States and 2% to 3% of people worldwide.1-3 Psoriasis is characterized by scaly, erythematous, pruritic plaques that can be painful and unsightly, with itch being the most prevalent and burdensome symptom.2,4 Although skin manifestations are the hallmark of psoriasis, it is considered to be a systemic inflammatory disease that often coexists with conditions such as psoriatic arthritis, obesity, and cardiovascular and psychiatric complications.2,5,6 The significant physical, psychological, and socioeconomic burdens experienced by patients with psoriasis can include an increased risk of anxiety, depression, and suicidal ideation.6-8
Psoriasis is primarily managed by dermatologists, nurse practitioners, and physician assistants specializing in dermatology, and also by rheumatologists and primary care physicians. Treatment is guided by disease severity measured by the extent and location of skin affected (eg, using the Physician Global Assessment [PGA]), and by evaluation of patients' own experiences.9
Most patients with plaque psoriasis have mild to moderate disease, and topical therapy is considered to be an appropriate treatment.5,10,11 In addition to their use in mild to moderate disease, topical therapies are often used as adjunctive treatment regardless of disease severity.11 Treatments indicated for moderate to severe psoriasis include oral systemic medications
