Pharm Aco Kin Etics, Safety, and Tolerability of Upadacitinib in Children with Atopic Dermatitis

ABSTRACT

BACKGROUND: Upadacitinib is a Janus kinase inhibitor that has been approved for the treatment of adults and adolescents with moderate to severe atopic dermatitis (AD). The objective of this study was to characterize the pharmacokinetics (PK), safety, and tolerability of upadacitinib in children with severe atopic dermatitis. METHOD(S) This is an open-label, multiple-dose study. AD patients (n = 35) were enrolled into four cohorts (Cohort 1, 6 to <12 years, low dose;Cohort 2, 6 to <12 years, high dose;Cohort 3, 2 to <6 years, low dose;Cohort 4, 2 to <6 years, high dose). The low and high doses were selected based on body weight to provide comparable plasma exposure in pediatrics to 15 mg and 30 mg QD doses in adults, respectively. All patients continued on the low dose after the PK assessment on Study Day 7. Safety and exploratory efficacy parameters are assessed in the study. RESULT(S) Geometric mean Cmax and AUC over 0-24 hours at steady state were 33.1 ng/mL and 249 ng.h/mL, respectively, in Cohort 1, 95.5 ng/mL and 523 ng.h/mL, respectively, in Cohort 2, 35.2 ng/mL and 264 ng.h/mL, respectively, in Cohort 3, and 101 ng/mL and 625 ng.h/mL, respectively, in Cohort 4. Upadacitinib was generally safe and well tolerated. The most common AEs were COVID infection, headache, and abdominal discomfort. No new safety risks were identified compared to the known safety profile for upadacitinib. In the 29 subjects with available interim efficacy results at week 12, 34.5% achieved validated Investigator's Global Assessment scale for AD score of 0 or 1 and 69.0% achieved Eczema Area and Severity Index by at least 75% at Week 12 with treatment of upadacitinib. CONCLUSION(S) The findings supported the use of current dosing regimens for further investigation of upadacitinib in upcoming phase 3 clinical trials in pediatric AD patients.