USA: Findings from two identical phase 3 trials showed the once-daily application of tapinarof 1% cream to be superior to vehicle control in reducing plaque psoriasis severity over a period of 12 weeks. However, the cream was associated with local adverse events and headaches. The study appears in the New England Journal of Medicine.
The authors stress the need for larger and longer trials for evaluating the safety and efficacy of tapinarof cream versus existing treatments for psoriasis.
Tapinarof cream is a topical aryl hydrocarbon receptor–modulating agent under investigation for psoriasis treatment. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin. Mark G. Lebwoh and the team conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis.
It included adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body surface area affected of 3 to 20%. They were randomly assigned in a ratio of 2:1 to receive tapinarof 1% cream or vehicle cream once daily for 12 weeks.
The primary endpoint was PGA response -- a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12.
Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score.
In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled.
Following were the study's key findings:
A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2.
Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point.
Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus.
"Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache," wrote the authors.
Reference:
The study titled, "Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis," is published in the New England Journal of Medicine.
DOI: https://www.nejm.org/doi/full/10.1056/NEJMoa2103629