Tapinarof in Atopic Dermatitis: Insights From Pooled Phase 3 Data

In this segment, Linda Stein Gold, MD, reviews pooled data presented at the 2026 Annual Meeting of the American Academy of Dermatology evaluating the efficacy and safety of tapinarof 1% cream in children and adults with atopic dermatitis (AD). The analysis combined findings from the ADORING 1 and ADORING 2 phase 3 clinical trials, providing a broader look at treatment outcomes across patients with moderate to severe disease.

Tapinarof and the aryl hydrocarbon receptor pathway

Dr Stein Gold begins by reviewing the background of tapinarof, a nonsteroidal topical therapy initially approved in 2022 for psoriasis in adults and later approved in 2024 for atopic dermatitis in patients as young as 2 years of age.

Tapinarof functions as an aryl hydrocarbon receptor agonist, representing a novel mechanism of action among topical therapies for AD. Activation of this pathway helps downregulate proinflammatory cytokines, including Th2 cytokines that play a central role in AD pathophysiology.  

ADORING 1 and ADORING 2 trial design

The pooled analysis incorporated data from ADORING1 and ADORING 2, two identically designed phase 3 studies conducted across different investigators, sites, and patients.

Eligible patients were 2 years of age or older with moderate to severe atopic dermatitis, an Eczema Area and Severity Index (EASI) score of at least 6, and body surface area (BSA) involvement ranging from 5% to 35%. Dr Stein Gold notes that patients at the higher end of the BSA range could reasonably be considered candidates for systemic therapy in routine practice. Average baseline BSA involvement across the studies was approximately 16% to 17%.

Participants were randomized in a 2:1 ratio to receive tapinarof 1% cream or vehicle once daily for 8 weeks. Investigators evaluated both efficacy and safety outcomes at the conclusion of treatment.

The primary endpoint focused on achieving clear or almost clear skin, defined as at least a 2-grade improvement. Additional endpoints included itch reduction, EASI50/75/90 responses, and other standard efficacy assessments.

Early efficacy signals observed by week 1

Dr Stein Gold highlights that separation between active treatment and vehicle was observed as early as week 1.

By week 8, nearly 46% of patients receiving tapinarof achieved clear or almost clear skin in the pooled analysis. Improvements continued consistently throughout the treatment period, with ongoing separation from vehicle across the 8-week study duration.

Itch reduction and low pruritus scores

The analysis also demonstrated early and sustained improvements in itch.

Investigators evaluated the standard ≥4-point reduction in peak pruritus numerical rating scale (NRS) scores and observed statistically significant separation from vehicle beginning at week 1. By week 8, just under 60% of patients achieved this level of itch improvement.

Dr Stein Gold also points to an additional itch endpoint that is less commonly evaluated in topical AD studies: achievement of a peak pruritus NRS score of 1 or lower, representing minimal or nearly absent itch. Separation from vehicle again emerged by week 1, and by week 8, nearly one-third of patients achieved this low itch threshold.

EASI responses across multiple thresholds

The pooled data also showed robust EASI responses over the course of treatment.

Separation from vehicle was observed as early as week 1 for both EASI50 and EASI75 responses. By week 8:

• ~78% of patients achieved EASI50  
• ~58% achieved EASI75  
• ~30% reached EASI90  

Safety profile remained consistent

From a safety standpoint, most treatment-emergent adverse events (TEAEs) were reported as mild to moderate in severity.

The most commonly reported adverse events included folliculitis, headache, upper respiratory infection, and nasopharyngitis. Discontinuation rates due to TEAEs remained low throughout the studies.

Expanding the topical treatment armamentarium in AD

In closing, Dr Stein Gold emphasizes that the pooled ADORING data demonstrate tapinarof cream to be a safe and effective nonsteroidal topical option for patients with moderate to severe atopic dermatitis, including pediatric patients down to age 2.

Key takeaways

• Pooled data from the ADORING 1 and ADORING 2 trials evaluated tapinarof 1% cream once daily in patients aged 2 years and older with moderate to severe atopic dermatitis  
• Tapinarof is a nonsteroidal aryl hydrocarbon receptor agonist that targets inflammatory pathways involved in AD  
• Separation from vehicle was observed as early as week 1 across multiple efficacy endpoints  
• By week 8, nearly 46% of patients achieved clear or almost clear skin  
• Just under 60% of patients achieved a ≥4-point itch reduction, and nearly one-third reached a peak pruritus NRS score of ≤1  
• Week 8 EASI responses included approximately 78% achieving EASI50, 58% achieving EASI75, and 30% achieving EASI90  
• Most treatment-emergent adverse events were mild to moderate, and discontinuation rates due to TEAEs were low