Article
作者: Yang, Wenlin ; Cao, Lei ; Pei, Xiaoping ; Ji, Chao ; Zhang, Li ; Yao, Weifeng ; Zhang, Litao ; Liang, Yunsheng ; Gao, Xinghua ; Lin, Bingjiang ; Feng, Wenli ; Xu, Aie ; Li, Linfeng ; Meng, Zudong ; Xie, Zhihong ; Jiang, Meiying ; Feng, Yanyan ; Bian, Kunpeng ; Zhang, Guoqiang ; Wang, Mingyue ; He, Yingxia ; Du, Daniel Y ; Wu, Liming ; Chen, Rixin
Background:A phase IIb clinical trial was conducted on pumecitinib (Synonyms: PG-011) gel as a novel selective Janus kinase (JAK)1/JAK2 inhibitor applied topically to treat atopic dermatitis (AD).
Objectives:To assess 3% pumecitinib gel for its efficacy and safety in treating mild-to-moderate AD adult patients and to determine its optimal treatment regimen.
Methods:In this study, 139 subjects with mild-to-moderate AD were randomized 1:1:1 to 3% pumecitinib BID (twice daily), QD (once daily) and placebo groups to undergo an 8-week treatment. The percentage change in Eczema Area and Severity Index (EASI) score from baseline at week 8 was the primary efficacy endpoint. The percentage of subjects with an IGA score of 0 or 1 (≥2 points improvement from baseline) at week 8, proportions of subjects attaining EASI-50, EASI-75, EASI-90 at week 8 and Quality of Life (QoL) improvement were also evaluated. Safety, local tolerability and sparsely sampled pharmacokinetics were monitored.
Results:At week 8, the percentage change from baseline in EASI score in pumecitinib BID, QD and placebo groups were -83.6%, -44.0% and -22.0%, respectively. Both pumecitinib treatment regimens showed significantly greater effect than placebo treatment (p<0.006) and the pumecitinib BID regimen had greater effect than the QD treatment (p<0.001). Compared to those in placebo group, other efficacy endpoints were also improved in the pumecitinib groups and the pumecitinib BID treatment consistently exhibited better efficacy than the QD treatment. For safety, total incidence rate of adverse events (AEs) in the pumecitinib and placebo groups were 48.4% and 47.8%, respectively. Safety profiles were generally similar between the pumecitinib and placebo groups and treatments were well tolerated. The mean plasma drug concentrations were low (range: 38–104 pg/mL) during 8 weeks of treatment.
Conclusions:The 3% pumecitinib gel showed good efficacy and safety profiles treating mild-to-moderate AD in adults. The pumecitinib BID treatment regimen demonstrated greater efficacy than the QD regiment to treat AD. Pumecitinib gel was well tolerated and generated low systemic drug exposure when used topically. It can be a new choice of topical JAK inhibitors for treating AD.