Exposure-Response Analyses for Upadacitinib Efficacy in Subjects With Atopic Dermatitis-Analyses of Phase 2b Study to Support Selection of Phase 3 Doses.
J Clin Pharmacol
; 61(5): 628-635, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33156550
ABSTRACT
Upadacitinib is a selective Janus kinase 1 inhibitor that was recently approved for treatment of rheumatoid arthritis and is currently being evaluated for treatment of several other autoimmune diseases, including atopic dermatitis (AD). The relationships between upadacitinib plasma exposure and efficacy (assessed as Eczema Area Severity Index [EASI]-75, EASI-90, and Investigator Global Assessment [IGA] 0/1) in subjects with moderate to severe atopic dermatitis were characterized using the data from 167 subjects who were enrolled in a phase 2b dose-ranging study. Subjects were randomized to receive once daily doses of monotherapy treatment with upadacitinib extended-release 7.5, 15, or 30 mg or placebo for 16 weeks. Logistic regression models were developed and utilized to simulate efficacy for upadacitinib with an approximate phase 3 sample size. Based on exposure-response models, 15 mg once daily is predicted to achieve EASI-75, EASI-90, and IGA 0/1 responses in 48%, 26%, and 29% of subjects, respectively, compared with placebo responses of 9%, 2%, and 2%, respectively, whereas 30 mg once daily is predicted to provide an additional approximately 20% greater efficacy for these end points relative to 15 mg once daily. These analyses supported the selection of upadacitinib doses that are being evaluated in ongoing global phase 3 studies in atopic dermatitis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antirheumatic Agents
/
Dermatitis, Atopic
/
Heterocyclic Compounds, 3-Ring
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Aspects:
Patient_preference
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Clin Pharmacol
Year:
2021
Document type:
Article
Affiliation country:
United States