Interplay between pharmacokinetics and immunogenicity of therapeutic proteins: stepwise development of a bidirectional joint pharmacokinetics-anti-drug antibodies model.

ABSTRACT: The aim of the analysis was to develop a phenomenological longitudinal population pharmacokinetics (PK)-anti-drug antibodies (ADA) model to enable an informed and quantitative framework for assessment of ADA influence. Data used were from seven clinical studies of avelumab across drug development phases in patients with several tumor types. ADA as covariate in a population PK model, and Markov models of ADA status (ADA+ or ADA-) were investigated. Finally, a joint PK-ADA model was developed. In the population PK models that evaluated ADA as a covariate, the clearance increase attributable to ADA+ status was 8.5% (time-varying ADA) to 19.9% (time-invariant ADA with inter-occasion variability in clearance). With a discrete-time Markov model (DTMM), tumor type was identified as a significant

SUBMITTER: van der Walt JS 

PROVIDER: S-EPMC12095442 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature