Results from 4 phase 1 trials indicate that 1% tapinarof cream — approved for psoriasis and being investigated for atopic dermatitis (AD) treatment — was well tolerated with no evidence of skin irritation among healthy adults. These study findings were published in the Journal of Drugs in Dermatology.
The 4 phase 1 trials were conducted to evaluate the irritation, sensitization, photoallergenicity, and phototoxicity profiles of tapinarof. In the first trial, 45 participants were randomly assigned to receive 1% tapinarof, vehicle, 0.9% saline, or 0.2% sodium lauryl sulfate applied in an occlusive patch on the back daily for 21 days. In the second trial, 240 patients were randomly assigned to receive 1% tapinarof, vehicle, or 0.9% saline applied in a semi-occlusive patch on the back 3 times per week for 3 weeks and following a 10 to 14-day rest period, a 48-hour single application sensitization challenge was conducted. In trial 3, 58 participants were randomly assigned to receive 1% tapinarof or vehicle applied in a semi-occlusive patch on the back twice a week for 3 weeks and following a 10 to 17-day rest period, 2 patches were applied, and 1 was challenged with irradiation exposure. In trial 4, 33 participants were randomly assigned to receive 1% tapinarof or vehicle applied in a semi-occlusive patch on the back on day 1 and on day 2, 2 patches were applied, and 1 was challenged with irradiation exposure.
The 4 trials included 376 participants who were aged mean 48.5 to 54.6 years of age. A total of 15 participants discontinued their trial.
The mean irritation score of tapinarof was 0.92 (standard deviation [0.66]) which was significantly higher than vehicle (mean, 0.02; P <.0001) and saline (mean, 0.10; P <.0001) and significantly lower than sodium lauryl sulfate (mean, 2.45; P <.0001). These scores indicated to researchers that there was no irritation from vehicle or saline, there was a slight potential for mild irritation from tapinarof, and a strong potential for mild to moderate irritation from sodium lauryl sulfate.
No patients had sensitization to tapinarof, vehicle, or saline. The percentage of patients who had a maximum sensitization score of 3, indicating erythema and papules, was 0.4% for tapinarof and 0.0% for vehicle and saline.
In the photoallergy trial, no evidence of photosensitization was observed. The maximum dermal response score was 1, indicating mild erythema or edema, and was observed among both tapinarof and vehicle recipients in both irradiated and nonirradiated patches.
Similarly, in the phototoxicity trial, no evidence of toxicity was observed. Mean dermal response scores in experimental patches with tapinarof that were irradiated were lower than vehicle or untreated irradiated sites. Overall, the irradiated patches had higher dermal response scores than nonirradiated patches for both tapinarof- (P =.0014) and vehicle- (P =.0044) treated areas.
In total, 4 treatment-emergent adverse events were reported, all of which were in the photoallergenicity trial, and none were related with the trial drug.
This analysis found that 1% tapinarof cream was well tolerated and did not demonstrate clinically meaningful irritation, sensitization, phototoxic, or photoallergic responses. “Tapinarof cream 1% once-daily may provide a first-in-class, nonsteroidal, topical therapeutic option for patients with psoriasis and AD that is highly effective and well tolerated,” investigators wrote. They continued, “The safety profile of tapinarof represents a substantial advantage over other topical products such as corticosteroids, retinoids, and vitamin D analogs,” as these topicals have restrictions on duration use and site and extent of application.
Disclosure: Several authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Jett JE, McLaughlin M, Wilson T, et al. Dermal safety of tapinarof cream 1%: results from 4 phase 1 trials. J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627