Difamilast ointment, a selective phosphodiesterase 4 inhibitor, in paediatric patients with atopic dermatitis: A phase 3 randomised double-blind, vehicle-controlled trial.

Abstract

BACKGROUND\nIn atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor.\n\n\nOBJECTIVES\nTo demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD.\n\n\nMETHODS\nThis was a phase 3 randomised, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0·3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks.\n\n\nRESULTS\nThe primary endpoint was the success rate in IGA score at week 4 (percentage of patients with IGA score of 0 or 1 with improvement by at least 2 grades). The success rates in IGA score at week 4 were 44·6%, 47·1%, and 18·1% in the difamilast 0·3%, difamilast 1%, and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score versus vehicle at week 4 (difamilast 0·3%, P = 0·0005; difamilast 1%, P < 0·0001). Regarding secondary endpoints, success rates in Eczema Area and Severity Index (EASI) 50, EASI 75 and EASI 90 at week 4 were significantly higher in difamilast 0·3% and 1% than those in vehicle. EASI score in difamilast 0·3% and 1% was significantly reduced compared with that of vehicle at week 1, and the significant difference between both difamilast and vehicle groups was maintained from week 1 through week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported.\n\n\nCONCLUSIONS\nDifamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.