Safety, pharmacokinetics, and efficacy of ruxolitinib cream in children and adolescents with atopic dermatitis.
Publication/Presentation Date
4-1-2023
Abstract
BACKGROUND: Therapies for children with atopic dermatitis (AD) have safety and tolerability concerns that may limit long-term use. Ruxolitinib cream, a Janus kinase (JAK) inhibitor, is effective and well tolerated in adolescents and adults with AD.
OBJECTIVE: To analyze the safety and tolerability of ruxolitinib cream in pediatric patients. Pharmacokinetics and efficacy were also evaluated in this phase 1 study (NCT03257644).
METHODS: Patients aged 2 to 17 years with AD (affected body surface area 8%-20%; Investigator's Global Assessment score ≥2) were enrolled stepwise in 6 age-descending, strength-increasing cohorts to apply 0.5%, 0.75%, or 1.5% ruxolitinib cream twice daily for 28 days. Safety, pharmacokinetics, and efficacy were analyzed at baseline, week 2 (day 10), and week 4 (day 29).
RESULTS: Among 71 patients, 44 (62.0%) had a baseline Investigator's Global Assessment score of 3; median (range) body surface area affected at baseline was 12.2% (1.7%-20.4%). Ruxolitinib cream was well tolerated, with 4 patients (5.6%) experiencing treatment-related adverse events (all grades 1/2). No clinically meaningful changes in mean chemistry or hematology values were observed, and no consistent pattern of change in bone biomarkers was detected. Mean plasma ruxolitinib levels within each cohort (range, 23.1-97.9 nM) were well below the half-maximal inhibitory concentration for thrombopoietin phosphorylation of STAT3 (281 nM). All cohorts experienced improvements in exploratory efficacy end points.
CONCLUSION: Ruxolitinib cream was well tolerated in pediatric patients with AD, with no effect on blood counts or bone biomarkers. Mean plasma concentration was low. Efficacy was consistent with data from previous studies in adolescents and adults.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03257644.
Volume
130
Issue
4
First Page
500
Last Page
507
ISSN
1534-4436
Published In/Presented At
Leung, D. Y. M., Paller, A. S., Zaenglein, A. L., Tom, W. L., Ong, P. Y., Venturanza, M. E., Kuligowski, M. E., Li, Q., Gong, X., & Lee, M. S. (2023). Safety, pharmacokinetics, and efficacy of ruxolitinib cream in children and adolescents with atopic dermatitis. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 130(4), 500–507.e3. https://doi.org/10.1016/j.anai.2022.12.033
Disciplines
Medicine and Health Sciences
PubMedID
36586583
Department(s)
Department of Medicine
Document Type
Article