Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial

J Am Acad Dermatol. 2022 Mar;86(3):607-614. doi: 10.1016/j.jaad.2021.10.027. Epub 2021 Oct 25.

Abstract

Background: Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis.

Objective: To demonstrate the superiority of difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis.

Methods: In this phase 3, randomized, double-blind trial, patients aged 15-70 years with an investigator global assessment score of 2 or 3 received topical difamilast ointment 1% (n = 182) or a vehicle (n = 182) twice daily for 4 weeks.

Results: The success rate in investigator global assessment score at week 4 (primary endpoint)-the percentage of patients achieving an investigator global assessment score of 0 or 1 with ≥2-grade improvement-was significantly higher with 1% difamilast than with the vehicle (38.46% vs 12.64%, respectively, P < .0001). The success rates in ≥50%, ≥75%, and ≥90% improvement in overall eczema area and severity index score at week 4 followed the same trend. Difamilast at 1% provided significant mean percent improvement from baseline in overall eczema area and severity index score versus vehicle from week 1 to 4. Treatment-emergent adverse events were mostly mild or moderate and less frequent with difamilast.

Limitations: Study treatment was limited to 4 weeks.

Conclusion: Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.

Keywords: MM36; OPA-15406; atopic dermatitis; difamilast; phosphodiesterase 4 (PDE4) inhibitor; topical therapies.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Benzamides
  • Dermatitis, Atopic* / chemically induced
  • Dermatitis, Atopic* / diagnosis
  • Dermatitis, Atopic* / drug therapy
  • Double-Blind Method
  • Eczema* / chemically induced
  • Emollients
  • Humans
  • Hyperplasia
  • Ointments
  • Phosphodiesterase 4 Inhibitors* / adverse effects
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Benzamides
  • Emollients
  • Ointments
  • Phosphodiesterase 4 Inhibitors
  • difamilast