Approval of Tapinarof Introduces New Class of Topical Treatments for Management of Plaque Psoriasis

Despite psoriasis being the most frequently experienced immune-mediated inflammatory skin disease, there is no known cure for it. Instead, current treatments are aimed at reducing the symptoms of psoriasis, which include dry, scaly, and itchy raised skin patches known as plaques. Plaque psoriasis, the most common form of psoriasis, occurs in more than 80% of all patients with psoriasis.^1,2

The complex pathophysiology is not clearly elucidated, but it is thought to consist of a feed-forward inflammatory mechanism involved in the pathway of T-helper cell type 17 (T_H17), part of the adaptive immune system.²

The amount, color, and severity of plaques vary among individuals and over time. Plaques are typically symmetrical and occur primarily on the elbows, knees, lower back, and scalp, where they often originate. In addition, the patches may present as different colors based on disease progression and skin color, with hyperpigmentation occurring during healing, particularly in darker-skinned individuals.

Flare-ups occur in a cyclic manner for a few weeks or months at a time.¹ Although the major cause of plaque psoriasis is polygenetic, resulting from the presence of multiple alleles and loci associated with psoriasis, environmental and behavioral factors may exacerbate the severity of symptoms in genetically predisposed individuals.

These factors include some infections (eg, streptococcal infection), certain medications (eg, β-blockers and nonsteroidal anti-inflammatory drugs), smoking tobacco, and stress. Trauma to the skin, which may include scratching or pressure from animal bites, sunburn, or skin lesions, can also create new or more severe plaques in a reaction known as the Koebner phenomenon.^2,3

Plaque psoriasis poses a significant burden to individuals. Moderate to severe psoriasis is associated with a 70% higher risk of developing comorbid conditions, including cardiometabolic diseases such as dyslipidemia, hypertension, vascular inflammation, and coronary atherosclerotic plaques, as well as obesity, diabetes mellitus, and anxiety and depression.^2,4

Approximately one-third of those with psoriasis develop psoriatic arthritis.²

There is also a substantial economic burden imposed by plaque psoriasis due to the frequency of inpatient and outpatient visits. Treatment is the highest contributor to costs, accounting for 37.5% of total disease-related spending for those with the disease.⁴ 

Different therapeutic options may be available to patients based on the degree of illness: mild plaque psoriasis is classified by localized rash covering less than 3% to 5% of the skin, while moderate to severe plaque psoriasis involves more extensive skin surface lesions.² The Physician’s Global Assessment (PGA) serves to quantify symptom severity on a scale from 0 to 4, with higher scores indicating more severe psoriasis.⁵

Topical therapies are typically the first course of action in treating mild psoriasis, and include topical corticosteroids, vitamin D analogs, calcineurin inhibitors, and keratolytics. Targeted phototherapy, which uses ultraviolet (UV) radiation to treat a small patch of affected skin, may also be used.

For moderate or severe psoriasis, phototherapy using UV-B or psoralen-UVA radiation suppresses DNA synthesis and expression involved in the pathology of the disease. Biological agents have been indicated for use in more serious disease states, and act as tumor necrosis factor-alpha (TNF-α) inhibitors, interleukin-12/23 (IL-12/23) inhibitors, interleukin-17 (IL-17) inhibitors, and interleukin-23 (IL-23) inhibitors.

There are also oral systemic agents, but these are typically prescribed only when patients have limited access to biologics or wish to avoid injectables, as they generally have lower efficacy than biological counterparts. Topical medications are often used in conjunction with other therapies in patients with moderate to severe plaque psoriasis.²

Tapinarof (Vtama) is a novel drug approved by the FDA in May 2022 and indicated for use in adults with any level of severity of plaque psoriasis.⁶ The first-in-class, steroid-free topical medication is an aryl hydrocarbon receptor antagonist whose mechanisms of action have not yet been made clear, but it is thought to bind the aryl hydrocarbon receptor, a ligand-dependent transcription factor that modulates T_H17 cell expression, skin barrier protein expression of filaggrin and loricrin keratinocytes, and antioxidant enzyme gene expression.⁵ Tapinarof cream 1% is indicated for topical use only and it is recommended to apply a thin layer to affected areas once daily.⁶ 

Tapinarof was approved following a phase 2b clinical trial that determined adequate dosage and efficacy, followed by PSOARING 1 (n = 510) and PSOARING 2: 2 identical, phase 3, multicenter, randomized, double-blind, vehicle-controlled trials. Participants aged 18-75 years (median age, 51) with moderate to severe plaque psoriasis, defined by baseline PGA scores of 2 (mild) to 4 (severe) on a scale of 0-4 and affected body surface area of 3%-20% were included in the study, with at least 80% of participants belonging to the “moderate” classification. Participants were randomly assigned in a 2:1 ratio to use tapinarof 1% or vehicle cream once daily for 12 weeks.^5,6

Improvement in plaque psoriasis, defined as a PGA score of 0 (clear) or 1 (almost clear) and a decrease by at least 2 points at week 12, was achieved by 35.4% and 40.2% of participants in the tapinarof groups and 6.0% and 6.3% of participants in the vehicle-controlled groups in PSOARING 1 and PSOARING 2, respectively. Adverse effects (AEs) experienced in both trials by the tapinarof group included headache, upper respiratory tract infection, and local events, such as folliculitis, nasopharyngitis, contact dermatitis, and pruritus.⁵

Those who completed 1 of the 2 studies were invited to participate in PSOARING 3, a long-term efficacy study. A total of 763 participants chose to continue in the study, which analyzed tolerability and duration of tapinarof 1%.⁷

After 40 weeks of open-label treatment with tapinarof 1%, it was found that 40.9% of patients experienced complete disease clearance (PGA = 0), with the mean duration following cessation of treatment of 130.1 days or 52 weeks with intermittent use. No tachyphylaxis was observed, and AEs were consistent with previous studies.⁷

Tapinarof, demonstrated to have lasting effects for a range of disease severities and with no significant AEs, can be used for adults with psoriasis either on its own or in combination with other therapies. Due to the unique mechanism of action of tapinarof compared with existing therapies, it may be effective in targeting the pathophysiology of psoriasis rather than symptoms alone.

Pharmacists treating patients with psoriasis should be aware of this novel class of medication and be prepared to address questions regarding its use. They should also continue to monitor for any local AEs and advise patients on appropriate application methods to maximize the effectiveness of this treatment. The efficacy of tapinarof in both short- and long-term studies on patients with varying baseline symptom severity shows that it is an option to take into consideration.

References

1. National Psoriasis Foundation. Plaque psoriasis. Accessed July 8, 2022. www.psoriasis.org/plaque 
2. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA. 2020;323(19):1945-1960. doi:10.1001/jama.2020.4006FDA.
3. Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug induced or drug aggravated? understanding pathophysiology and clinical relevance. J Clin Aesthet Dermatol. 2010;3(1):32-38.
4. Lee S, Xie L, Wang Y, Vaidya N, Baser O. Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population. J Med Econ. 2018;21(6):564-570. doi:10.1080/13696998.2018.1431921
5. Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 trials of tapinarof cream for plaque psoriasis. N Engl J Med. 2021;385(24):2219-2229. doi:10.1056/NEJMoa2103629
6. Vtama. Prescribing information. Dermavant Sciences, Inc; 2022. Accessed June 17, 2022. www.vtama.com/docs/DMVT_VTAMA_PI.pdf
7. Strober B, Gold LS, Bissonnette R, et al. Tapinarof cream 1% once daily for plaque psoriasis: long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent. SKIN: J Cutaneous Medicine. 2022;6(2):s5. Poster. Accessed July 15, 2022. https://jofskin.org/index.php/skin/article/view/1521/pdf