In a recent trial, Difamilast 03% and 1% ointments were found to be superior to vehicles and well tolerated in Japanese pediatric patients with Atopic dermatitis (AD). In AD, inhibiting phosphodiesterase 4 (PDE4) lowers proinflammatory mediators and cytokines. Difamilast is a novel PDE4 inhibitor.
This study was conducted by H. Saeki and team with the objective to demonstrate the advantage of topical difamilast over vehicle in Japanese pediatric AD patients. The findings of this study were published in the British Journal of Dermatology on 21st July, 2021.
This was a randomized, double-blind, vehicle-controlled phase III experiment. Patients aged 2–14 years with an Investigator Global Assessment (IGA) score of 2 or 3 were given difamilast 03% (n = 83), difamilast 1% (n = 85), or vehicle (n = 83) ointment two times a day, daily for 4 weeks. The main outcome was the proportion of patients with an IGA score of 0 or 1 who improved by at least two grades by week four.
The key findings of this study were as follow:
1. At week 4, the success rates in IGA score were 44.6%, 47.1%, and 18.1% in the difamilast 0.3%, difamilast 1%, and vehicle groups, respectively.
2. At week 4, both difamilast groups had significantly better success rates in IGA score compared to the vehicle [difamilast 03% (P 0001); difamilast 1% (P 0001)].
3. In terms of secondary objectives, improvements in Eczema Area and Severity Index (EASI; 50%, 75%, and 90% improvement in overall score) at week 4 were substantially higher in patients in the difamilast 0.3% and 1% groups than in those in the vehicle group.
4. At week 1, the EASI score in the difamilast 0.3% and 1% groups was considerably lower than that of those in the vehicle group.
5. From week 1 to week 4, the substantial difference between the difamilast and vehicle groups was maintained.
6. The majority of treatment-emergent adverse events were mild to moderate in severity, with no severe events or fatalities reported.
In conclusion, because there is presently no cure for AD, topical medicines and emollients are the cornerstone of treatment for juvenile children with the disease. Because safety and tolerability are critical variables, particularly for pediatric patients, choosing medicine with fewer safety issues is critical. Although the results of existing and future trials are awaited, difamilast looks to have promise as a novel therapeutic option for pediatric children with AD, with high and quick effectiveness and a favorable tolerability profile.
Reference:
Saeki, H., Baba, N., Ito, K., Yokota, D. and Tsubouchi, H. (2022), Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial*. Br J Dermatol, 186: 40-49. https://doi.org/10.1111/bjd.20655