Tapinarof safe, efficacious for moderate-to-severe AD in children, adults

Treatment with tapinarof cream 1% once daily demonstrates significant efficacy with a favourable safety profile among adults and children with moderate-to-severe atopic dermatitis (AD), a study has shown. 

"Tapinarof potentially fills a gap in the treatment armamentarium for a highly effective, nonsteroidal topical that can be used down to 2 years of age without restrictions on the severity of disease, duration of use, total body surface area treated, or sites of application,” the investigators said.  

This study examined the efficacy and safety of tapinarof in adults and kids up to 2 years of age with AD. Overall, 813 patients were randomly assigned to receive tapinarof cream 1% or vehicle once daily in two 8-week phase III trials. 

Both trials significantly met the primary efficacy endpoints, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at week 8 (tapinarof vs vehicle: 45.4 percent vs 13.9 percent for trial 1 and 46.4 percent vs 18.0 percent for trial 2; p<0.0001 for both). [J Am Acad Dermatol 2024;91:457-465] 

Similarly, tapinarof was superior to vehicle in terms of Eczema Area and Severity Index 75 responses at week 8 (trial 1: 55.8 percent vs 22.9 percent; trial 2: 59.1 percent vs 21.2 percent; p<0.0001 for both). The study agent also showed significantly rapid improvements in patient-reported pruritus. 

The most common adverse events were folliculitis, headache, and nasopharyngitis, most of which were either mild or moderate in severity. In addition, the tapinarof groups in the two trials exhibited lower discontinuations due to adverse events relative to the vehicle groups. 

“Tapinarof was well tolerated in patients down to 2 years of age, demonstrating a favourable and predictable safety profile, consistent with previous trials in AD and plaque psoriasis,” the investigators said. [N Engl J Med 2021;385:2219-2229; J Am Acad Dermatol 2022;87:800-806; J Am Acad Dermatol 2019;80:89-98.e3; J Am Acad Dermatol 2021;84:632-638] 

Furthermore, tapinarof demonstrated efficacy across a diverse population, with an age range of 2 to 81 years, and about 50 percent with skin of color based on self-reported race and Fitzpatrick skin type. 

Long-term efficacy 

"[T]he long-term extension trial, ADORING 3, will assess the efficacy and safety of tapinarof cream in AD across the spectrum of severity, including patients with mild or more severe AD, and assessment of the potential remittive effect observed in both a phase IIb trial in AD and a long-term phase III trial in plaque psoriasis,” the investigators said. 

“Eligible participants from ADORING 1 and 2 who enrolled in the long-term extension trial, ADORING 3, will be evaluated for up to 48 weeks,” they added. [J Am Acad Dermatol 2022;87:800-806; J Am Acad Dermatol 2019;80:89-98.e3; J Am Acad Dermatol 2021;84:632-638] 

A topical aryl hydrocarbon receptor agonist, tapinarof downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. [J Am Acad Dermatol 2024;91:457-465]