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

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 was <2‐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.