Characterization of anti-drug antibody dynamics using a bivariate mixed hidden-markov model by nonlinear-mixed effects approach.

ABSTRACT: Biological therapies may act as immunogenic triggers leading to the formation of anti-drug antibodies (ADAs). Population pharmacokinetic (PK) models can be used to characterize the relationship between ADA and drug disposition but often rely on the ADA bioassay results, which may not be sufficiently sensitive to inform on this characterization.In this work, a methodology that could help to further elucidate the underlying ADA production and impact on the drug disposition was explored. A mixed hidden-Markov model (MHMM) was developed to characterize the underlying (hidden) formation of ADA against the biologic, using certolizumab pegol (CZP), as a test drug. CZP is a PEGylated Fc free TNF-inhibitor used in the treatment of rheumatoid arthritis and other chronic inflammatory diseases.The biv

SUBMITTER: Brekkan A 

PROVIDER: S-EPMC10884144 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature