What Did Japanese and US Difamilast Trials Find?

Which trials were compared?

Double-blind trials compared 1% difamilast twice daily for four weeks with vehicle, the ointment without difamilast, for mild-to-moderate atopic dermatitis. Japan randomized 364 participants, eligible ages 15–70; the US randomized 153, aged two or older.¹

What counted as improvement?

Week-four success required clear or almost clear skin plus at least a two-grade improvement on the clinician’s scale. FDA’s¹ review reports:¹

Trial	Difamilast	Vehicle
Japan	70/182	23/182
US	11/94	7/59

Adjusted differences were 25.9 percentage points (95% CI 17.5–34.4) in Japan and −0.2 (−13.2 to 9.0) in the US. Missing scores counted as failures. US results do not establish equivalence.¹

How should the contrast be read?

US recruitment stopped for business reasons at 153 of 336 planned. Definitions and populations differed; the reasons remain unclear. FDA¹ accepted other Japanese and multinational results while acknowledging US uncertainty. Sponsors were drug companies; investigator financial disclosures were missing at 16 sites.¹

What does the current US prescription cover?

The ADQUEY label, revised February 2026, covers mild-to-moderate atopic dermatitis in adults and children aged two or older. It specifies a thin layer twice daily, washing hands afterward, and avoiding infected skin. It is not for eyes, mouth or vaginal use. Have the prescriber check a new rash before treating it as eczema.²

The label reports nose-and-throat symptoms and less common local reactions including contact dermatitis, folliculitis and rash. Application-site swelling has been reported after approval; voluntary reports cannot establish its frequency or prove causation. New swelling or irritation belongs in the prescribing review.²

Pregnancy data are insufficient to assess risk. During breastfeeding, do not apply directly to the nipple or areola, and prevent the baby’s skin contacting treated areas. Discuss pregnancy plans and feeding with the clinician.²

In “Your First Thirty Days, and the Next Twelve Weeks,” Skin, Head to Toe puts the clinician’s plan first. Its Skin Log dates product starts, photographs and irritation. Use that record for the agreed prescription review; the book’s calendar for self-chosen products does not replace it.