Delgocitinib cream formulation demonstrates a dose-dependent response in adults with mild to severe atopic dermatitis: results from an 8-week randomised Phase IIb trial

BACKGROUND: Delgocitinib is a topical, pan-Janus kinase (JAK) inhibitor that targets all four members of the JAK family. In patients with atopic dermatitis (AD), delgocitinib ointment 0.5% resulted in improved efficacy compared with vehicle ointment and a favourable safety profile. OBJECTIVES: This double-blind, cream vehicle-controlled Phase IIb trial (NCT03725722) investigated the dose-response relationship, efficacy, and safety of delgocitinib cream in adults with mild to severe AD. METHODS: Adults with mild to severe AD were randomised 1:1:1:1:1 to delgocitinib cream 1, 3, 8, 20 mg/g or cream vehicle. Delgocitinib cream or cream vehicle were applied twice daily on the areas affected by AD for 8 weeks. The primary endpoint was change from baseline to week 8 in Eczema Area and Severity Index (EASI). Exploratory key secondary endpoints included Validated Investigator's Global Assessment for AD treatment success (vIGA-AD TS; defined as score of 0 [clear] or 1 [almost clear] with a ≥2-step improvement from baseline to week 8) and EASI-75 (≥75% improvement in EASI from baseline) at week 8. Safety was assessed throughout. RESULTS: Overall, 251 patients were randomised (delgocitinib cream groups: n=201; cream vehicle: n=50). At week 8, treatment with delgocitinib cream resulted in dose-dependent change in EASI scores from baseline versus cream vehicle (1 mg/g: -5.0; 3 mg/g: -4.9; 8 mg/g: -5.8; 20 mg/g: -7.6; all P<0.05 vs cream vehicle [-1.9]). A greater proportion of delgocitinib cream-treated patients achieved vIGA-AD TS (1 mg/g: 18.4%; 3 mg/g: 29.2%; 8 mg/g: 30.0%; 20 mg/g: 48.0%) than those in the cream vehicle group (10.4%) at week 8. EASI-75 was seen in 40.8% (1 mg/g), 43.8% (3 mg/g), 56.0% (8 mg/g) and 66.0% (20 mg/g) and 20.8% (cream vehicle) of patients at week 8. The incidence of adverse events was similar with delgocitinib cream (44.5%) and cream vehicle (56.0%), with most frequently reported adverse events (≥5.0% in any treatment group) being upper respiratory tract infection, AD, acne, headache, and application site pruritus. CONCLUSIONS: Treatment with delgocitinib cream was more effective than cream vehicle in a dose-response manner for the primary and secondary endpoints. Delgocitinib cream was well tolerated and no safety concerns were identified.