Population Pharmacodynamic Model of Neutrophil Margination and Tolerance to Describe Effect of Sarilumab on Absolute Neutrophil Count in Patients with Rheumatoid Arthritis.

ABSTRACT: Evidence suggests that effects of interleukin-6 pathway inhibitors sarilumab, tocilizumab, and sirukumab on absolute neutrophil count (ANC) are due to margination of circulating neutrophils into rapidly mobilizable noncirculating pools. We developed a population pharmacodynamic model using compartments for neutrophil margination and ANC-specific tolerance to describe rapid, transient ANC changes in blood following administration of subcutaneous sarilumab and intravenous/subcutaneous tocilizumab based on data from 322 patients with rheumatoid arthritis in two single-dose (NCT02097524 and NCT02404558) and one multiple-dose (NCT01768572) trials. The model incorporated a tolerance compartment to account for ANC nadir and beginning of recovery before maximal drug concentration after subcutaneou

SUBMITTER: Kovalenko P 

PROVIDER: S-EPMC7376291 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature