Topical pan-JAK inhibitor cream safe and efficacious in atopic dermatitis

Delgocitinib cream was surprisingly effective in a randomised, multi-dose, vehicle-controlled trial that included adult patients with atopic dermatitis: two-thirds of patients treated with the highest dose had a >75% improvement in the Eczema Area and Severity Index (EASI 75).

The agent delgocitinib is a broad-spectrum JAK inhibitor blocking signal pathways including JAK-1/2/3 and tyrosine kinase 2. In a previous study, delgocitinib was successful in patients with chronic hand eczema.

The study presented during the AAD VMX 2021 meeting was a randomised, vehicle-controlled, dose-ranging phase 2b trial involving adults with atopic dermatitis (AD) of at least 1-year duration (NCT03725722) [1]. Eligible patients had a mean body surface area (BSA) affected by AD of 10 and disease severity according to the investigators global assessment (IGA) ranging from mild to severe. Patients were treated with a vehicle cream or delgocitinib cream in 4 different doses (i.e. 1, 3, 8, and 20 mg/g), which was applied twice daily. The primary endpoint of the study was the change in EASI score from baseline to week 8.

Included in the analysis were 251 patients. In the highest dose group (20 mg), EASI score dropped by 7.6 from baseline to week 8 compared with 1.9 in the placebo group (P<0.05). With regard to change from baseline in EASI score, all delgocitinib doses separated distinctly from the vehicle arm by week 1, which continued up to week 8. “Clearly, the highest dose had the greatest efficacy,” Prof. Jonathan Silverberg (George Washington University, Washington DC, USA) emphasised during his presentation. The EASI 75 response rate at week 8 showed a similar pattern. In the highest dose group, this difference became significant as early as week 1 compared with the control group. Treatment with delgocitinib was accompanied by a significant improvement in the quality of life, assessed in the Dermatology Life Quality Index (DLQI).

“Itch is the most common and most burdensome symptom in AD,” Prof. Silverberg said. In this study, itch relief was assessed as secondary endpoint: patients had a baseline itch score of 6.1, which decreased by 4.6 points in the highest dose group by week 8 and by 2.8–3.0 point in the other delgocitinib arms, compared with 1.0 in the placebo group (P<0.05). Daily itch score declined significantly versus the control group by day 2 in all but the lowest dose of delgocitinib. The safety profile of the JAK inhibitor was comparable to that of the control group.

1. Silverberg J, et al. The topical pan-JAK inhibitor delgocitinib in a cream formulation is efficacious with a favorable safety profile: results from an 8-week phase 2b dose-ranging trial in atopic dermatitis. AAD VMX 2021, 23-25 April.

Copyright ©2021 Medicom Medical Publishers



Posted on 7 June 202116 February 2024