Tapinarof in Atopic Dermatitis: Early Clinical Responses and the Role of AhR Agonism

In this installment of Discourses in Dermatology, Seemal R. Desai, MD, discusses advances in aryl hydrocarbon receptor (AhR) agonism and highlights new data presented at Fall Clinical 2026 examining early clinical responses to tapinarof cream 1% in patients with atopic dermatitis (AD).

Tapinarof, a first-in-class, nonsteroidal topical AhR agonist, is FDA approved for once-daily treatment of AD in adults and children aged 2 years and older.

Early clinical improvement: findings from the ADORING trials

New data from a pooled analysis of the phase 3 ADORING 1 and ADORING 2 trials evaluated individual patient responses to tapinarof cream 1% over time. Of the 813 randomized patients, 80.4% were children, and all had moderate to severe AD at baseline.

The analysis demonstrated early clinical responses observed with tapinarof, with a significant response versus vehicle in validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) response rates as early as Week 1 and sustained through Week 8.

Individual Eczema Area and Severity Index (EASI) responses also demonstrated early improvement:

• Week 1: 84.6% of tapinarof-treated patients demonstrated some degree of EASI improvement from baseline

• Week 2: 92.0% of tapinarof-treated patients demonstrated some degree of EASI improvement from baseline

• Week 8: 96.9% of tapinarof-treated patients demonstrated measurable EASI improvement from baseline

These percentages reflect the proportion of patients experiencing any improvement in EASI scores.

By Week 8, EASI50, EASI75, and EASI90 response rates were 83.4%, 62.7%, and 32.8%, respectively, with tapinarof, compared with 46.6%, 25.6%, and 9.4% with vehicle (all P<0.0001).

Dr Desai highlights the value of examining individual patient responses at different time points, particularly the early changes in disease severity and the broader implications for understanding treatment response.

AhR agonism: addressing inflammation and skin barrier function

Beyond the clinical findings, Dr Desai discusses the mechanism of AhR agonism and its relevance to AD management.

AhR is an intracellular ligand-activated transcription factor involved in regulating inflammatory responses and epidermal barrier function. Dr Desai describes these processes using a seesaw analogy, emphasizing the importance of balancing inflammation control with restoration of the skin barrier.

Through AhR activation, tapinarof modulates inflammatory signaling, including pathways associated with type 2 inflammation, while promoting processes involved in epidermal barrier repair and normalization.

This dual activity is particularly relevant in AD, where inflammation and skin barrier dysfunction contribute to symptoms such as pruritus, burning, cracking, and fissuring.