Tapinarof Tolerability in Psoriasis and Atopic Dermatitis: Follicular Events, Contact Dermatitis, and Clinical Perspective

In this episode of Topical Conversations, Linda Stein Gold, MD, and G. Michael Lewitt, MD, discuss the tolerability profile of tapinarof and how adverse events observed in clinical trials compare with their real-world experience treating patients with plaque psoriasis and atopic dermatitis.

Tapinarof, an aryl hydrocarbon receptor (AhR) agonist, was initially approved in 2022 for adults with plaque psoriasis and was subsequently approved for atopic dermatitis in patients as young as 2 years of age. Through modulation of AhR signaling, tapinarof influences multiple pathways relevant to inflammatory skin disease, including cytokine signaling, oxidative stress, and skin barrier function.

The discussion focuses on two adverse events that have received particular attention: follicular events and contact dermatitis.

Tapinarof and the evolving role of nonsteroidal topical therapy

Historically, nonsteroidal topical therapies have often been incorporated into treatment regimens as adjunctive agents or during topical corticosteroid holidays, helping patients maintain disease control while reducing reliance on corticosteroids.

Dr Lewitt notes that tapinarof has been used somewhat differently in clinical practice, serving not only as a maintenance therapy but also as a treatment capable of achieving disease control in appropriate patients. Dr Stein Gold agrees that the availability of newer nonsteroidal topical options has allowed for simpler treatment approaches in some patients, reducing the need for multiple topical medications with different roles within a treatment regimen.

Tolerability profile of tapinarof

Both physicians note that application-site stinging and burning have been relatively uncommon in their experience with tapinarof, particularly compared with some earlier nonsteroidal topical therapies.

Instead, the adverse events most frequently discussed in relation to tapinarof have been follicular events and contact dermatitis. While these events have been observed in both psoriasis and atopic dermatitis clinical trials, the incidence, severity, and clinical significance warrant closer examination.

Folliculitis in plaque psoriasis

Dr Lewitt reviews findings from the psoriasis clinical trials, where folliculitis was reported in approximately 18% to 24% of patients during the 12-week treatment period.

Importantly, the majority of cases were not characterized by inflammatory pustular lesions. Rather, they were more commonly described as hyperkeratotic or keratosis pilaris-like follicular changes. Most events were mild to moderate in severity, and treatment discontinuation due to folliculitis was uncommon.

Follicular events in atopic dermatitis

The physicians contrast these findings with those observed in the atopic dermatitis trials, where follicular events were designated as an adverse event of special interest.

In the 8-week atopic dermatitis trials, follicular events occurred less frequently than in the psoriasis studies, with reported rates of approximately 9% to 14%. As in the psoriasis trials, most events were mild to moderate in severity; discontinuation rates were below 1%.

Dr Lewitt notes that his real-world experience has generally aligned with the clinical trial findings, with follicular events appearing less common among patients with atopic dermatitis than among patients with psoriasis. Dr Stein Gold reports a similar experience, noting that she has not observed folliculitis among her own patients with atopic dermatitis treated with tapinarof.

Contact dermatitis: incidence and clinical considerations

Contact dermatitis has also been reported during tapinarof treatment.

Dr Lewitt notes that in the psoriasis clinical trials, contact dermatitis occurred in approximately 5% to 6% of patients, with discontinuation rates of approximately 1.5%. Based on the clinical characteristics of these reactions, he speculates that at least some cases may have represented irritant rather than allergic contact dermatitis.

In the atopic dermatitis trials, rates of contact dermatitis were low, with both event rates and discontinuation rates below 1%. Notably, contact dermatitis was reported more frequently in the vehicle arm than in the tapinarof-treated arm.

Dr Stein Gold notes that she has encountered contact dermatitis infrequently in clinical practice, reporting a single case among her patients with psoriasis and none among her patients with atopic dermatitis.

Practical considerations for clinical use

Neither physician views follicular events or contact dermatitis as a major barrier to prescribing tapinarof. Both note that these adverse events are generally uncommon, typically mild to moderate in severity, and infrequently lead to treatment discontinuation.

Dr Lewitt notes that when discussing treatment expectations with patients, he mentions the possibility of these adverse events while emphasizing their generally manageable nature. Practical measures such as applying a thin layer of medication, minimizing application to occluded areas, wearing loose-fitting clothing when appropriate, and applying tapinarof after an emollient may help reduce the likelihood of unwanted drug spread to uninvolved skin.

Clinical perspective

The discussion highlights that while follicular events and contact dermatitis can occur during tapinarof treatment, both events are typically mild to moderate in severity and rarely result in treatment discontinuation. The incidence of these adverse events appears lower in atopic dermatitis clinical trials than in psoriasis studies, and both physicians report real-world experiences that generally align with those observations.

For clinicians considering nonsteroidal topical treatment options for chronic inflammatory skin disease, understanding the nature and clinical relevance of these adverse events may help inform treatment selection and patient discussions.