Efficacy and safety of pumecitinib 3% gel in treating mild-to-moderate atopic dermatitis: a multicentre randomized double-blind parallel placebo-controlled phase IIb clinical trial.

Abstract

We conducted a phase IIb clinical trial of pumecitinib 3% gel (PG-011), a novel selective Janus kinase (JAK)1/2 inhibitor, applied topically to treat mild-to-moderate atopic dermatitis (AD). To assess pumecitinib 3% gel for its efficacy and safety in treating adult patients with mild-to-moderate AD, and to determine the optimal treatment regimen. In this study, 139 participants with mild-to-moderate AD were randomized 1 : 1 : 1 to pumecitinib 3% gel twice daily (n = 47), pumecitinib 3% gel once daily (n = 46) and placebo (n = 46) for 8 weeks of treatment. Percentage change in Eczema Area and Severity Index (EASI) score from baseline to week 8 was the primary efficacy endpoint. The percentage of participants with an Investigator's Global Assessment score of 0 or 1 (≥ 2-point improvement from baseline) at week 8, the proportion of participants attaining ≥ 50% improvement in EASI (EASI 50), ≥ 75% improvement in EASI (EASI 75) and ≥ 90% improvement in EASI (EASI 90) at week 8, and improvement in quality of life were also evaluated. Safety, local tolerability and some pharmacokinetics were monitored. At week 8, the percentage change from baseline in EASI score in the pumecitinib 3% gel twice daily, pumecitinib 3% gel once daily and placebo groups was -83.6%, -44.0% and -22.0%, respectively. Both pumecitinib treatment regimens showed a significantly greater effect compared with placebo (P < 0.006) and the pumecitinib 3% gel twice-daily regimen had a greater effect than once-daily treatment (P < 0.001). Other efficacy endpoints were also improved in participants in the pumecitinib groups vs. those in the placebo group, and pumecitinib 3% gel twice daily consistently exhibited better efficacy than the once-daily treatment. With regard to safety, the rate of adverse events in the pumecitinib and placebo groups was 48% and 48%, respectively. Safety profiles were generally similar between the pumecitinib and placebo groups, and treatment was well tolerated. Mean plasma drug concentrations were low (range 38-104 pg mL-1) over the 8-week treatment period. Pumecitinib 3% gel showed good efficacy and safety profiles in the treatment of adults with mild-to-moderate AD. The pumecitinib 3% twice-daily treatment regimen showed greater efficacy than the once-daily regimen in treating mild-to-moderate AD. Pumecitinib 3% gel was well tolerated and generated low systemic drug exposure when used topically. It may be a new choice of topical JAK inhibitor to treat mild-to-moderate AD.