Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial

Background In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor. Objectives To demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD. Methods This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0 center dot 3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks. Results The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44 center dot 6%, 47 center dot 1% and 18 center dot 1% in the difamilast 0 center dot 3%, difamilast 1% and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [difamilast 0 center dot 3% (P < 0 center dot 001); difamilast 1% (P < 0 center dot 001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of >= 50%, >= 75% and >= 90% in overall score) at week 4 were significantly higher in patients in the difamilast 0 center dot 3% and 1% groups than those in the vehicle group. EASI score in the difamilast 0 center dot 3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported. Conclusions Difamilast 0 center dot 3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.