Difamilast 1% ointment was superior to vehicle for improving Investigator Global Assessment (IGA) scores in patients with atopic dermatitis (AD), according to phase 3 study findings published in the Journal of the American Academy of Dermatology.

The multicenter study included 364 Japanese adult patients (mean age, 31.9±10.7 years) with a 3-year or greater history of AD (mean duration since onset, 24.8±11.2 years) and IGA scores of 2 (14.6%) or 3 (85.4%). All patients had an AD-affected body surface area (BSA) of 5% to 40%.

Patients were randomly assigned to either difamilast 1% ointment (n=182) or the identical vehicle control ointment (n=182), both of which were applied twice daily for 4 weeks. The treatment success rate, assessed at 4 weeks, was defined by the percentage of patients who achieved an IGA score of 0 or 1 with corresponding improvement of 2 or more grades. At week 4, the success rate was significantly higher in patients assigned to difamilast 1% ointment compared with those assigned to vehicle (38.5% vs 12.6%, respectively; difference, 25.9%; 95% CI, 17.46-34.40; P <.0001).


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In addition, the researchers assessed the 4-week success rate using the Eczema Area and Severity Index (EASI) 50, EASI 75, and EASI 90, representing the percentage of patients who had 50% or greater, 75% or greater, and 90% or greater improvements in overall EASI score, respectively, at week 4. Success rates were significantly higher for difamilast 1% ointment in EASI 50 (58.2% vs 25.8%; respectively; P <.0001), EASI 75 (42.86% vs 13.19%; P <.0001), and EASI 90 (24.73% vs 5.49%; P <.0001).

The least squares (LS) mean change in the Verbal Rating Scale for pruritus score from baseline to week 4 was greater in patients assigned to difamilast 1% ointment (–0.65 vs –0.04; difference, –0.61; 95% CI, –0.80 to –0.42) P <.0001). At week 4, treatment with difamilast 1% ointment was also associated with a greater LS mean change in the Patient-Oriented Eczema Measure score (-3.23 vs 0.70; difference, –3.93; 95% CI, –5.25 to –2.61; P <.001), overall Skindex-16 score (-15.20 vs -1.23; difference, –13.97; 95% CI, –18.33 to –9.60; P <.0001) and each subscale score, as well as the total affected BSA (-6.11 vs -0.09; difference, -6.02; 95% CI, -8.45 to -3.60; P <.0001).

Treatment-emergent adverse events (TEAEs) were reported in 17.6% of patients in the difamilast 1% ointment arm and 28% of patients assigned to vehicle. Most TEAEs were mild or moderate in severity with worsening AD (3.8% for difamilast 1% vs 12.1% for vehicle). There were no serious adverse events or deaths in either treatment arm.

A limitation of the study included its relatively short treatment duration. The researchers wrote that a long-term trial (NCT03961529) “will provide further information regarding efficacy and safety of difamilast.”

Disclosure: This clinical trial was supported by Otsuka Pharmaceutical. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Saeki H, Ito K, Yokota D, Tsubouchi H. Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized double-blind vehicle-controlled trial. J Am Acad Dermatol. Published online October 25, 2021. doi:10.1016/j.jaad.2021.10.027