2019 PharmSci 360
The consequences of immunogenicity can vary from no clinically relevant effects, to substantial effects on pharmacokinetics (PK), pharmacodynamics (PD), and potentially safety. Particularly for drugs which show a high incidence of immunogenicity as measured by sensitive analytical ADA assays; there is an interest in relating the quality of the immune response (onset, magnitude, and duration) to relevant effects on PK in subjects with positive samples. We propose a modeling-based approach where a quantitative output of the ADA assay (the ratio of signal to noise [S/N]) can be used as a covariate to describe effects of immunogenicity on exposure. This presentation will explore a case study of the relationships of ADA assay magnitude and duration of a detectable immune response with effects on the PK of a monoclonal antibody. The goal is to present a framework for including more granular ADA assay detail in PK models.