Saeki Hidehisa, Ito Kensuke, Yokota Daisuke, Tsubouchi Hidetsugu
Department of Dermatology, Nippon Medical School, Tokyo, Japan.
Headquarters of Clinical Development, Otsuka Pharmaceutical Co Ltd, Osaka, Japan.
J Am Acad Dermatol. 2022 Mar;86(3):607-614. doi: 10.1016/j.jaad.2021.10.027. Epub 2021 Oct 25.
Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis.
To demonstrate the superiority of difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis.
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.
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.
Study treatment was limited to 4 weeks.
Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.
地法米司特是一种选择性磷酸二酯酶4抑制剂。磷酸二酯酶4参与与炎症性疾病（包括特应性皮炎）相关的细胞因子产生。
在成年日本特应性皮炎患者中证明1%地法米司特软膏相对于赋形剂的优越性。
在这项3期随机双盲试验中，年龄在15 - 70岁、研究者整体评估评分为2或3的患者，每天两次外用1%地法米司特软膏（n = 182）或赋形剂（n = 182），持续4周。
在第4周时研究者整体评估评分的成功率（主要终点）——达到研究者整体评估评分为0或1且改善≥2级的患者百分比——1%地法米司特组显著高于赋形剂组（分别为38.46%和12.64%，P <.0001）。在第4周时，湿疹总面积和严重程度指数评分改善≥50%、≥75%和≥90%的成功率也呈现相同趋势。从第1周到第4周，1%地法米司特组相对于赋形剂组在湿疹总面积和严重程度指数评分方面从基线的平均改善百分比显著更高。治疗中出现的不良事件大多为轻度或中度，且地法米司特组的发生率较低。
研究治疗限于4周。
1%地法米司特软膏在成年日本特应性皮炎患者中显示出相对于赋形剂的优越性及良好的安全性。
