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The first trial observing the topical drug in children held promise for an extended indication.
Once-daily tapinarof cream 1% was associated with minimal, if any, systemic exposure in pediatric or adolescent patients with extensive atopic dermatitis, according to new findings from a maximal usage trial.1
In an abstract presented at the Maui Derm 2023 NP + PA Summer Conference in Colorado Springs this week, a team of US investigators reported a positive, safe pharmacokinetic profile of the aryl hydrocarbon receptor agonist when used to treat atopic dermatitis in children and adolescents.
The trial—the first to report use of tapinarof cream in children ≤12 years old, at a dose regimen approved by the US Food and Drug Administration (FDA) for adults with plaque psoriasis—precedes further analysis data into the drug’s benefit for pediatric atopic dermatitis, anticipated for some time this year.
Led by Amy S. Paller, MD, Chair of the Department of Dermatology at Northwestern Feinberg School of Medicine, investigators sought to evaluate the pharmacokinetics, tolerability, and safety of once-daily tapinarof cream 1% in adolescents and children ≥2 years old with atopic dermatitis. The topical agent was approved by the FDA to treat adults with psoriasis in May 2022;2 Paller and colleagues noted its profile across previous adult trials was characterized by “minimal to no systemic absorption and decreasing plasma concentrations over the course of treatment.”
The team enrolled adolescents and children into a trio of age cohorts: 2 – 6 years old; 7 – 11 years old; 12 – 17 years old. Eligible patients had a validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) score of ≥3 and body surface area (BSA) involvement of either ≥25%—for those aged 12 – 17 years old—or ≥35%—for those aged 2 – 11 years old. Each cohort was administered tapinarof cream 1% once-daily for 4 weeks.
Investigators sought primary endpoints including pharmacokinetic parameters, Local Tolerability Scale (LTS) scores for both overall and sensitive skin areas during clinician visits, and treatment-emergent adverse events (TEAEs).
The trial included 36 patients, with each cohort represented by 12 children and adolescents. Mean patient age was 8.9 years old; two-thirds of patients were male. More than three-fourths (77.8%) of patients had a baseline vIGA-AD score of 3; mean baseline BSA was 42.8%; mean Eczema Area and Severity Index (EASI) score was 23.8.
Paller and colleagues observed little to no tapinarof systemic exposure in treated patients. Their mean maximum plasma concentration at 4 weeks was 2.4 ng/mL, and median time to maximum concentration was approximately 3 hours.
One-fourth of post-treatment plasma samples were below the limit of the study’s highly sensitive assay; the team observed no association between tapinarof exposure baseline BSA score affected. Mean overall skin LTS score was 0.1 at both weeks 1 and 4, indicating no irritation. A majority of patients reported no irritation on sensitive or intertriginous skin while receiving tapinarf.
Eight (22%) patients reported a TEAE; all were mild or moderate in severity. One patient discontinued therapy due to 2 unrelated TEAEs. Investigators reported no cases of contact dermatitis. A significant majority (87.5%) opted in to the 48-week long-term extension trial for the drug.
The team concluded that the initial assessment into pediatric patients showed tapinarof cream 1% was not linked to any significant systemic exposure, even when measured against a highly sensitive assay.
“There was a low incidence of TEAEs in patients with up to 90% BSA affected,” they concluded. “Tapinarof cream was well tolerated, including on sensitive and intertriginous skin areas.”