Tapinarof cream effective regardless of AD severity, age in two trials

Once-daily application of tapinarof cream 1% significantly improves the Eczema Area Severity Index (EASI) score in patients with atopic dermatitis (AD), regardless of their disease severity or age, according to the pivotal phase III ADORING 1 and 2 trials presented at AAAAI 2024.

Tapinarof cream 1%, a nonsteroidal, topical aryl hydrocarbon receptor agonist, is FDA-approved for the treatment of plaque psoriasis in adults, according to Dr Luz Fonacier from NYU Long Island School of Medicine in Mineola, New York, US.

The ADORING 1 and 2 phase III studies enrolled 407 and 406 patients with moderate-to-severe AD, respectively, with a mean baseline EASI score of 12.2─13.5. Approximately 80 percent of the participants were children aged 2–17 years. The participants were randomized in a 2:1 ratio to receive either tapinarof cream 1% (ADORING 1: n=270, ADORING 2: n=271) or vehicle (ADORING 1: n=137, ADORING 2: n=135) once daily for 8 weeks.

By week 8, a significantly higher percentage of patients treated with tapinarof cream 1% achieved a ≥75 percent improvement in EASI score (EASI75) from baseline in both the ADORING 1 (55.8 percent vs 22.9 percent; p<0.0001) and ADORING 2 studies (59.1 percent vs 21.2 percent; p<0.0001) compared with the vehicle group. [AAAAI 2024, abstract 014]

Significantly more tapinarof- vs vehicle-treated patients also achieved higher EASI75 response rates, regardless of whether they had moderate (58.8 percent vs 25.7 percent [ADORING 1] and 59.9 percent vs 24.3 percent [ADORING 2]) or severe AD (54.5 percent vs 6.9 percent [ADORING 1] and 69.3 percent vs 7.6 percent [ADORING 2]).

Furthermore, across all age subgroups, patients who received tapinarof cream consistently demonstrated significantly higher EASI75 response rates than those who received vehicle.

In the children cohort, treatment with tapinarof cream 1% resulted in a higher EASI75 response rate at week 8 among those aged 2–6 years (72.1 percent vs 17 percent [ADORING 1] and 68.1 percent vs 24.8 percent [ADORING 2]), 7–11 years (52.1 percent vs 28 percent [ADORING 1] and 55.3 percent vs 35.1 percent [ADORING 2]), and 12–17 years (54.3 percent vs 24.5 percent [ADORING 1] and 68.1 percent vs 13.5 percent [ADORING 2]) compared with vehicle.

Similarly, among the adult cohort (aged ≥18 years), the EASI75 response rate was higher in the tapinarof arm than in the vehicle arm (52.5 percent vs 26.2 percent [ADORING 1] and 49.2 percent vs 15.1 percent [ADORING 2]).

Safety profile

The most common treatment-emergent adverse events (TEAEs) observed were folliculitis, headache, and nasopharyngitis, but all were considered mild or moderate in severity.

There was a lower rate of TEAEs that led to trial discontinuations with tapinarof compared with vehicle in ADORING 1 (1.9 percent vs 3.6 percent) and ADORING 2 (1.5 percent vs 3.0 percent).

Tapinarof was well tolerated, and TEAEs were consistent with those observed in previous trials, Fonacier noted.

“Overall, tapinarof cream 1% once daily demonstrated consistent, clinically meaningful efficacy regardless of AD severity, or the age of the patient at baseline, in two large well-controlled phase III trials,” said Fonacier.

“Tapinarof [has] the potential for use in the treatment of AD in patients down to 2 years of age without restrictions on duration, extent, or sites of application,” she noted.