Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study

Hidehisa Saeki; Tomomi Imamura; Daisuke Yokota; Hidetsugu Tsubouchi

doi:10.1007/s13555-022-00751-9

Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study

Dermatol Ther (Heidelb). 2022 Jul;12(7):1589-1601. doi: 10.1007/s13555-022-00751-9. Epub 2022 Jun 18.

Authors

Hidehisa Saeki¹, Tomomi Imamura², Daisuke Yokota³, Hidetsugu Tsubouchi⁴

Affiliations

¹ Department of Dermatology, Nippon Medical School, Tokyo, Japan.
² Headquarters of Clinical Development, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
³ Headquarters of Clinical Development, Otsuka Pharmaceutical Co., Ltd., Osaka, Japan.
⁴ Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 3-2-27 Otedori, Chuo-ku, Osaka, 540-0021, Japan. Tsubouchi.Hidetsugu@otsuka.jp.

Abstract

Introduction: Phosphodiesterase 4 (PDE4), which regulates inflammatory cytokine production leading to atopic dermatitis (AD), is selectively inhibited by difamilast. The objective of this phase III, long-term, open-label study was to evaluate the safety and efficacy of topical difamilast in Japanese adult and pediatric patients with AD.

Methods: Adult patients (n = 166) began treatment with difamilast 1% ointment, and pediatric patients began treatment with difamilast 0.3% ointment (n = 144) or difamilast 1% ointment (n = 56). Treatment was continued twice daily for 52 weeks. All patients had an Investigator's Global Assessment (IGA) score of 2 (mild), 3 (moderate), or 4 (severe/very severe), and an AD-affected body surface area (BSA) of ≥ 5% before treatment, with no restriction on the upper limit for the AD-affected BSA.

Results: During therapy, 120 adult patients (72.3%) and 178 pediatric patients (89.0%) experienced treatment-emergent adverse events (TEAEs), most of which were mild or moderate in severity. Discontinuation due to TEAEs was reported in 13 adult patients (7.8%) and in 7 pediatric patients (3.5%). Treatment-related adverse events were reported in 14 adult patients (8.4%) and 16 pediatric patients (8.0%), most frequently dermatitis atopic (1.8%) and acne (1.2%) in adult patients and dermatitis atopic and pigmentation disorder (each 2.0%) in pediatric patients. The cumulative success rates in Eczema Area and Severity Index (EASI)-75 in adult and pediatric patients were 55.4% and 73.5%, respectively, at week 52, and the cumulative success rates increased from week 4 to week 52. The cumulative success rates in IGA score showed the same trend as those in EASI -75.

Conclusions: This study demonstrates that difamilast ointments are well tolerated and effective in Japanese adult and pediatric patients with AD when applied twice daily for 52 weeks, and are expected to be used for a long-term treatment for AD.

Clinical trial registration: Clinical Trials.gov identifier: NCT03961529.

Keywords: Application; Atopic dermatitis; Difamilast; Japanese adult and pediatric patients; Ointment; Open-label study; Phosphodiesterase 4; Safety.

Associated data

ClinicalTrials.gov/NCT03961529