(eg, methotrexate, cyclosporine, apremilast, deucravacitinib, and acitretin), biologic therapies (including inhibitors of tumor necrosis factor-alpha, interleukin [IL]-12/IL-23, IL-23, and IL-17), and phototherapy.5,9,12,13 Certain topical therapies are associated with restrictions on duration, extent, and site of application, and with local irritation and other adverse events (AEs).11 Adherence challenges and low patient satisfaction with topical therapies can also be due to frequency and difficulty of application, the associated time burden, and properties of the formulation and vehicle, such as texture and odor.14-16
Here, we review the development of tapinarof (VTAMA®; Dermavant Sciences, Inc.), a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor (AhR) agonist approved by the US Food and Drug Administration (FDA) in May 2022 for the treatment of plaque psoriasis in adults, and under investigation for the treatment of psoriasis in children down to 2 years of age and for atopic dermatitis (AD) in adults and children down to 2 years of age.
History of Psoriasis Treatments
Progress in the development of psoriasis treatments over the last 50 years is summarized in Figure 1. Until recently, the only FDA-approved topical treatments for psoriasis were corticosteroids, vitamin D analogs, and retinoids.11,17 Although these therapies may be efficacious, especially for short-term treatment of localized disease, they have limitations based on affected body surface area, duration of use, and location of application.11 Use of corticosteroids may also be limited by the potential for skin atrophy, recurrence of symptoms after cessation of treatment, tachyphylaxis, and patient and/or prescriber aversion/fear of their use.11,18 Other topical agents, including calcipotriene and tazarotene, have modest efficacy as monotherapies and well-documented AEs, including erythema and skin irritation.11,19
NOVEL TOPICAL THERAPY
Development of Tapinarof
The discovery of tapinarof was a fortuitous outcome of in-vestigations into secondary metabolites of a bioluminescent bacterium, Photorhabdus luminescens, which lives symbi-otically in soil-living nematode worms that parasitize insects.17 Insects infected by the nematodes did not decay after death and the investigator hypothesized that metabolites produced by the bacteria were responsible for this effect.17 One metabolite was purified and identified as 3,5-dihydroxy-4-isopropylstilbene (tapinarof), which demonstrated anti-inflammatory properties
