By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved a first-in-class, nonsteroidal, topical, aryl hydrocarbon receptor agonist to treat plaque psoriasis.1 Tapinarof cream is distributed as Vtama.
INDICATIONS
Tapinarof can be prescribed to treat plaque psoriasis in adults.2
DOSAGE
Apply a thin layer to affected areas once daily.2 Tapinarof is available as a 60 g topical cream, with each gram containing 10 mg of tapinarof.
POTENTIAL ADVANTAGES
Tapinarof offers a first-in-class aryl hydrocarbon receptor agonist with a novel mode of action for the topical treatment of psoriasis.
POTENTIAL DISADVANTAGES
The most frequently reported (tapinarof vs. vehicle) adverse reaction is folliculitis (20% vs. 1%).2 Approximately 3% of subjects in the clinical trial test subjects discontinued treatment because of dermatitis or folliculitis.2 Along with local reactions, headache and nasopharyngitis also were reported.2
COMMENTS
In patients with psoriasis, dysregulated aryl hydrocarbon receptor expression has been shown, making the receptor a target for treatment.3 Tapinarof downregulates proinflammatory cytokines (e.g., interleukin-17) and promotes skin barrier normalization. The efficacy and safety of tapinarof were evaluated in two identical, randomized, double-blind, vehicle-controlled trials that included 1,025 adults, 82% of whom presented with moderate psoriasis (PSOARING 1 and 2).2,4 Those with < 3% or > 20% of body surface affected were excluded. Subjects were randomized in a 2:1 ratio to tapinarof or vehicle cream for 12 weeks. The primary efficacy endpoint was the proportion of subjects who achieved treatment success, defined as “Clear” or “Almost Clear” on a five-point Physician Global Assessment (PGA) scale and at least a two-grade improvement from baseline. Eighty-two percent of subjects exhibited moderate disease (PGA score of 3) and 8% reported severe disease (PGA score of 4). Treatment success rates at week 12 (PGA = 0 or 1) were 36% and 40% for tapinarof vs. 6% for both vehicle treatment. Subjects who completed the trials were eligible for a long-term (up to 52 weeks) open-label trial (PSOARING 3; n = 763).5 Those with complete disease clearance discontinued treatment, those with PGA ≥ 1 continued treatment until treatment clearance, and those with worsening disease (PGA ≥ 2) restarted treatment.
Maximum effect may not be achieved by week 12, as 58% of subjects with PGA ≥ 2 achieved success (i.e., PGA = 0 or 1) at least once during the open-label trial. The authors did not observe evidence of tachyphylaxis. The duration of efficacy maintained after treatment is discontinued (remittive effect) is about four months, and there were no new safety signals. In a maximal use trial, subjects with a body surface area involvement of ≥ 20% and daily application for 29 days had low systemic exposure, with 68% of samples demonstrating tapinarof levels below detectable (< 50 pg/mL).6
CLINICAL IMPLICATIONS
Psoriasis is a common inflammatory disease, affecting approximately 3.2% of the population.7 Topical treatment is the mainstay, with up to 80% experiencing mild-to-moderate psoriasis, which can be managed generally with topical treatments.7 The list of topical options is long. It includes corticosteroids, off-label use of calcineurin inhibitors (tacrolimus, pimecrolimus), vitamin D analogues (e.g., calcipotriene), and tarzarotene.7 While all these are effective and safe, all carry drawbacks. Topical corticosteroids have been associated with skin atrophy, striae, and possible tachyphylaxis. Skin irritation is associated with calcineurin inhibitors, vitamin D analogues, and tazarotene.7 The latter is contraindicated in pregnancy. Tapinarof provides a topical drug with a novel mode of action. Its ultimate role will be determined by comparative studies with existing topical therapy. The cost for tapinarof cream is $1,325 for a 60-g tube.
REFERENCES
1. Roivant Sciences. FDA approves Dermavant’s VTAMA® (tapinarof) cream, 1% for the treatment of plaque psoriasis in adults: First topical novel chemical entity launched for psoriasis in the U.S. in 25 years. May 24, 2022.
2. Dermavant Sciences, Inc. Vtama prescribing information. May 2022.
3. Bissonnette R, Stein Gold L, Rubenstein DS, et al. Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent. J Am Acad Dermatol 2021;84:1059-1067.
4. Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 trials of tapinarof cream for plaque psoriasis. N Engl J Med 2021;385:2219-2229.
5. Strober B, Stein Gold L, Bissonnette R, et al. One-year safety and efficacy of tapinarof cream for the treatment of plaque psoriasis: Results from the PSOARING 3 trial. J Am Acad Dermatol 2022; Jun 27:S0190-9622(22)02219-8. doi: 10.1016/j.jaad.2022.06.1171. [Online ahead of print].
6. Jett JE, McLaughlin M, Lee MS, et al. Tapinarof cream 1% for extensive plaque psoriasis: A maximal use trial on safety, tolerability, and pharmacokinetics. Am J Clin Dermatolol 2022;23:83-91.
7. Elmets CA, Korman NJ, Prater EF, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol 2021;84:432-470.
Tapinarof can be prescribed to treat plaque psoriasis in adults.
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