Population approach for exposure-response modeling of golimumab in patients with rheumatoid arthritis

Journal of Clinical Pharmacology
Chuanpu HuHonghui Zhou

Abstract

Golimumab is a human immunoglobulin G1κ monoclonal antibody that binds with high affinity and specificity to tumor necrosis factor-α. The objective of this study was to establish an approach for exposure-response modeling for golimumab in patients with rheumatoid arthritis using the American College of Rheumatology index of improvement (ACRN) as a measure of change in disease severity. Data were collected from 302 patients in the phase III GO-FORWARD trial who received golimumab or placebo plus methotrexate (background therapy) every 4 weeks through week 52. A latent-variable (unobservable) approach was used with an inhibitory indirect response model to link the placebo (methotrexate) effect and golimumab concentrations to ACRN scores. A model parameterization was proposed to allow deterioration beyond baseline and maintain mechanistic interpretability of the population-based indirect response model. The modeling was conducted using a sequential pharmacokinetic/pharmacodynamic approach. None of the covariate factors evaluated (demographics, disease characteristics, comorbidities, or concomitant medications) significantly improved the model fits. Likelihood profiling and a bootstrap analysis were used to assess parameter estimat...Continue Reading

References

May 1, 1992·British Journal of Rheumatology·F M BrennanM Feldmann
Feb 7, 1998·Journal of Pharmaceutical Sciences·W Krzyzanski, W J Jusko
Nov 30, 2000·The New England Journal of Medicine·J M BathonB K Finck
May 30, 2002·Nature Reviews. Immunology·Marc Feldmann
Mar 6, 2004·Journal of Pharmacokinetics and Pharmacodynamics·Liping ZhangLewis B Sheiner
Oct 5, 2007·Annual Review of Pharmacology and Toxicology·B J Anderson, N H G Holford
Nov 21, 2007·Annals of Internal Medicine·Katrina E DonahueKathleen N Lohr
Jan 1, 2008·Arthritis and Rheumatism·Charles G HelmickUNKNOWN National Arthritis Data Workgroup
May 21, 2008·Journal of Clinical Pharmacology·Chuanpu Hu, Honghui Zhou

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Citations

Nov 13, 2012·Critical Reviews in Biomedical Engineering·Hoi-Kei LonWilliam J Jusko
Dec 19, 2015·Expert Review of Clinical Pharmacology·A S StrikM Löwenberg
Mar 10, 2017·Expert Review of Gastroenterology & Hepatology·Anne S StrikMark Löwenberg
May 10, 2017·Therapeutic Drug Monitoring·Gilles PaintaudDenis Mulleman
Aug 15, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Leonid Kagan
Dec 19, 2016·British Journal of Clinical Pharmacology·Carla BastidaDolors Soy
May 29, 2018·Clinical Pharmacokinetics·David TernantGilles Paintaud
Nov 1, 2013·Therapeutic Innovation & Regulatory Science·Russell ReeveWei Xiao

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