Long-term tapinarof use proven safe, effective in plaque psoriasis

Continuous and intermittent use of tapinarof cream 1% once daily (QD) for up to 1 year is effective in patients with mild-to-severe plaque psoriasis, without serious safety concerns, according to a study. In addition, it has shown durable efficacy and a remittive effect of at least 4 months off therapy.

“Consequently, tapinarof cream 1% QD may represent a novel, nonsteroidal topical therapy for patients with plaque psoriasis that is effective and well tolerated with long-term use,” the researchers said.

Previously, two 12-week phase III trials in adults with mild-to-severe plaque psoriasis demonstrated the efficacy and safety of the aryl hydrocarbon receptor-modulating agent tapinarof cream 1% over vehicle. Those who completed these trials were eligible for 40-weeks’ open-label treatment and 4-weeks’ follow-up to assess the long-term safety, efficacy, remittive effect, durability, and tolerability of tapinarof.

Treatment was based on the Physician Global Assessment (PGA) score, and patients with PGA≥1 were administered tapinarof until complete disease clearance (PGA=0). Those who had achieved PGA=0 discontinued treatment and were then monitored for remittive effect. On the other hand, patients with PGA≥2 underwent retreatment until they reached PGA=0.

A total of 763 patients met the eligibility criteria, of whom 40.9 percent achieved complete disease clearance, while 58.2 percent who entered with PGA≥2 achieved PGA=0 or 1. [J Am Acad Dermatol 2022;87:800-806]

For patients who achieved complete disease clearance, the mean duration of off-therapy remittive effect was 130.1 days. No new safety concerns arose. Folliculitis (22.7 percent) was the most frequent adverse event, followed by contact dermatitis (5.5 percent) and upper respiratory tract infection (4.7 percent).

Tachyphylaxis, which was been observed with topical corticosteroids and biologics, did not take place with tapinarof for up to 52 weeks. This finding supported that of previous phase II and III trials. [J Am Acad Dermatol 2021;84:432-470; Am J Clin Dermatol 2022;23:83-91; N Engl J Med 2021;385:2219-2229; Ann Rheum Dis 2005;64:ii83-ii86; Semin Cutan Med Surg 2016;35:S78-S80]

The remittive effective with tapinarof could have been driven by its specific binding and activation of AhR, a ligand-dependent transcription factor, according to the researchers. [J Am Acad Dermatol 2021;84:1059-1067]

“AhR activation has been shown to inhibit T-cell expansion and T helper 17 (Th17) cell differentiation and reduce IL-17 production in T-cell assays,” they said. [J Invest Dermatol 2017;137:2110-2119]

“Ligand-dependent AhR activation has also been demonstrated to result in epigenetic modification of both the forkhead box P3 (FoxP3) and IL-17 gene promoters, leading to preferential differentiation of regulatory T cells and inhibition of Th17 cells,” the researchers added. [PLoS One 2011;6e23522]

Furthermore, earlier studies have shown that long-term persistence of tissue-resident memory T cell is AhR dependent, and that the remittive effect with tapinarof may have also been caused by the reduced activity of these cells. [Proc Natl Acad Sci U S A 2014;111:5307-5312; J Invest Dermatol 2022;doi:10.1016/j.jid.2022.05.1011]

The current study was limited by its open-label design and the absence of a control group. In addition, results could not be generalized to all forms of psoriasis, and the remittive effect/response rate was potentially underestimated, according to the researchers.