Tapinarof a new kid on the block for plaque psoriasis
Treatment with the nonsteroidal topical cream tapinarof 1% for up to 52 weeks helps control plaque psoriasis in the phase III PSOARING 3 trial.
Tapinarof is a small-molecule aryl hydrocarbon receptor (AhR) modulating agent currently under US FDA review for plaque psoriasis in adults. Modulation of AhR signaling is thought to reverse immune dysregulation involved in plaque psoriasis. The disease is characterized by dry, raised, red skin patches or lesions on the elbows, knees, lower back, and scalp that are covered with silvery scales. Plaque psoriasis goes through cycles, flaring for weeks or months, then going into remission. Treatment can help manage the symptoms.
“[But] currently available nonsteroidal topical therapies are typically associated with significant irritation,” said study author Dr Linda Stein Gold, director of dermatology clinical research, Henry Ford Health System, Detroit, Michigan, US during her presentation at EADV 2021. “We did not see that with tapinarof.”
3 trials of tapinarof
The new data from PSOARING 3 build on the success of the PSOARING 1 and PSOARING 2 trials of adult patients with plaque psoriasis treated with tapinarof 1% or a vehicle. Both studies had the primary endpoint of the proportion of patients who achieved a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear), with a minimum 2-grade improvement at week 12 from baseline.
The proportion of patients who achieved 0/1 scores with tapinarof 1% was 35.4 percent in the PSOARING 1 trial and 40.2 percent in the PSOARING 2 trial (p<0.0001 for both), compared with 6 percent for placebo in both trials, said Gold. The advantage of tapinarof over placebo was comparable even for the key secondary endpoint of ≥75 percent improvement in the Psoriasis Area and Severity Index (PASI75).
Over 90 percent of patients from both trials continued with tapinarof 1% for 52 weeks in PSOARING 3.
The median duration of a remittive effect was 115 days in the 79 patients who entered the extension study with a PGA score of 0 and who were off treatment, whereas the mean remittive effect after discontinuing therapy was 130 days in those with a higher PGA score but achieved a score of 0 during the study (312 patients). [EADV 2021, abstract 2860]
There was no loss of effect despite intermittent therapy nor tachyphylaxis, Gold said. Folliculitis was the most common treatment-emergent adverse event reported (24 percent), followed by contact dermatitis (5.9 percent) and headache (2 percent).
Finally, a first in its class?
“A potential first-in-class nonsteroidal, tapinarof cream may be useful for patients who are looking for topical therapy for sensitive areas like the skin folds or the face,” said Gold.
“Rather than its potential for application to sensitive areas, to me, the durability of effect is more interesting,” commented Dr Adam Friedman from the Department of Dermatology at George Washington School of Medicine and Health Sciences in Washington, DC, US. “Many psoriasis patients have 'been there and done that' when it comes to topical steroids. An effective and well-tolerated nonsteroidal topical option is a welcome development for patients who have been suffering from steroid phobia.”