Integrated Exposure-Response of Dupilumab in Children, Adolescents, and Adults With Atopic Dermatitis Using Categorical and Continuous Efficacy Assessments: A Population Analysis.
atopic dermatitis
dupilumab
exposure–response
pediatrics
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
received:
31
05
2023
accepted:
27
09
2023
medline:
12
12
2023
pubmed:
12
12
2023
entrez:
11
12
2023
Statut:
aheadofprint
Résumé
While the majority of patients with atopic dermatitis (AD) achieve disease control with dupilumab treatment, there is variability in which patients achieve clear disease. The predictors of these responses are currently unclear. Integrated models were developed to evaluate the exposure-response (E-R) relationship of dupilumab in children, adolescents, and adults with AD. Data from six Phase II and III clinical studies were pooled (2,366 adults [> 18 years], 243 adolescents [≥ 12 to < 18 years] and 359 children [≥ 6 to < 12 years]) for model development. Efficacy was assessed using the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA). Indirect response models were applied to link measures of efficacy and functional serum dupilumab concentrations. The covariates on individual placebo-corrected response were assessed. Clinical trial scenarios were simulated to compare E-R relationships across age groups. Safety was not explored. After correcting for differences in placebo response and dupilumab exposure: 1) older age, higher body weight, lower baseline thymus and activation-regulated chemokine, and Asian race were associated with slightly lower EASI response, and no clear covariates were identified on IGA response; 2) clinical trial simulations generally showed slightly higher response at a given dupilumab concentration in children compared to adults and adolescents with severe and moderate AD. The collectively tested covariates explain some of the variability in dupilumab response in patients with AD. Patients in all age groups showed adequate response to dupilumab; however, children showed slightly higher drug effects compared to adults and adolescents at equivalent concentrations.
Sections du résumé
BACKGROUND
BACKGROUND
While the majority of patients with atopic dermatitis (AD) achieve disease control with dupilumab treatment, there is variability in which patients achieve clear disease. The predictors of these responses are currently unclear. Integrated models were developed to evaluate the exposure-response (E-R) relationship of dupilumab in children, adolescents, and adults with AD.
METHODS
METHODS
Data from six Phase II and III clinical studies were pooled (2,366 adults [> 18 years], 243 adolescents [≥ 12 to < 18 years] and 359 children [≥ 6 to < 12 years]) for model development. Efficacy was assessed using the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA). Indirect response models were applied to link measures of efficacy and functional serum dupilumab concentrations. The covariates on individual placebo-corrected response were assessed. Clinical trial scenarios were simulated to compare E-R relationships across age groups. Safety was not explored.
RESULTS
RESULTS
After correcting for differences in placebo response and dupilumab exposure: 1) older age, higher body weight, lower baseline thymus and activation-regulated chemokine, and Asian race were associated with slightly lower EASI response, and no clear covariates were identified on IGA response; 2) clinical trial simulations generally showed slightly higher response at a given dupilumab concentration in children compared to adults and adolescents with severe and moderate AD.
CONCLUSIONS
CONCLUSIONS
The collectively tested covariates explain some of the variability in dupilumab response in patients with AD. Patients in all age groups showed adequate response to dupilumab; however, children showed slightly higher drug effects compared to adults and adolescents at equivalent concentrations.
Identifiants
pubmed: 38082089
doi: 10.1007/s11095-023-03616-8
pii: 10.1007/s11095-023-03616-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s).
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