Population‐Based Pharmacokinetic and Exposure‐Efficacy Analyses of Peginterferon Beta‐1a in Patients With Relapsing Multiple Sclerosis. (10th April 2017)

• Record Type: Journal Article
• Authors: Hu, Xiao; Hang, Yaming; Cui, Yue; Zhang, Jie; Liu, Shifang; Seddighzadeh, Ali; Deykin, Aaron; Nestorov, Ivan
• Is Part Of: Journal of clinical pharmacology. Volume 57:Number 8(2017)
• Page Start: 1005
• Page End: 1016
• Publication Date: 2017-04-10
• Subjects: interferon beta‐1a -- pegylation -- pharmacometric analysis -- count data -- annualized relapse rate; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.883
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: Peginterferon beta‐1a reduced annualized relapse rate as compared with placebo and was approved to treat multiple sclerosis patients. A population pharmacokinetic and an exposure‐efficacy model were developed to establish the quantitative relationship between pharmacokinetics and annualized relapse rate. The pharmacokinetics was well described by a 1‐compartment model with first‐order absorption and linear elimination kinetics. Body mass index was the most significant covariate that impacted both clearance and volume of distribution, which in turn impacted area under the curve and maximum serum concentration. Cumulative monthly area under the curve and annualized relapse rate were best described by a Poisson‐gamma (negative binomial) model, demonstrating that the improved efficacy of every‐2‐weeks dosing was driven by greater drug exposure. The results supported the superior efficacy of the every‐2‐week dosing regimen compared with the every‐4‐weeks dosing regimen.