Population Pharmacokinetics of Tralokinumab in Adult Subjects With Moderate to Severe Atopic Dermatitis

Autor: Anders, Soehoel, Malte Selch, Larsen, Stine, Timmermann
Rok vydání: 2022
Předmět:
Zdroj: Clinical Pharmacology in Drug Development. 11:910-921
ISSN: 2160-7648
2160-763X
DOI: 10.1002/cpdd.1113
Popis: Tralokinumab is the first biologic therapy for moderate-to-severe atopic dermatitis (AD) that specifically neutralizes interleukin-13 activity, a key driver of AD signs and symptoms. Tralokinumab is a human immunoglobulin G4 monoclonal antibody administered subcutaneously every 2 weeks (with possibility of maintenance dosing every 4 weeks). This population pharmacokinetic (PK) analysis aimed to identify sources of PK variability and relevant predictors of tralokinumab exposure in adults with moderate to severe AD. Nonlinear mixed-effect modeling, including covariate analysis, was used on a data set including 2561 subjects (AD, asthma, healthy) from 10 clinical trials. A 2-compartment model with first-order absorption and elimination adequately described the tralokinumab PK. Body weight was identified as a relevant predictor of tralokinumab exposure; other covariates including age, sex, race, ethnicity, disease type, AD severity, and renal and hepatic impairment were not. For body weight, the difference in exposure between the upper- and lower-weight quartiles in patients with AD was2-fold, supporting the appropriateness of flat dosing (300 mg). Given the reduced exposure associated with higher body weight, coupled with the reduced exposure provided by dosing every 4 weeks, it is uncertain whether higher-weight patients will achieve sufficient exposure to maintain efficacy if dosed every 4 weeks instead of the standard every 2 weeks.
Databáze: OpenAIRE
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