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DDMODEL00000123: Ait-Oudhia_2012_Rheumatoid_Arthritis_Canakinumab

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Bridging Clinical Outcomes of Canakinumab Treatment in Patients With Rheumatoid Arthritis With a Population Model of IL-1beta Kinetics
PharmML (0.6.1)
  • Bridging Clinical Outcomes of Canakinumab Treatment in Patients With Rheumatoid Arthritis With a Population Model of IL-1? Kinetics.
  • Ait-Oudhia S, Mager DE, Lowe P
  • CPT: pharmacometrics & systems pharmacology, 1/2012, Volume 1, pages: e5
  • Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
  • Canakinumab, an anti-interleukin-1? (IL-1?) monoclonal antibody, is approved for cryopyrin-associated periodic syndromes and is under investigation for the management of other inflammatory disorders. In this study, population-based pharmacokinetic-pharmacodynamic models were developed to understand responses to canakinumab in patients with rheumatoid arthritis (RA). Total canakinumab and total IL-1? concentrations were obtained from four clinical trials (n = 472). In contrast to traditional models, free IL-1? concentrations were calculated and used to link canakinumab to changes in C-reactive protein (CRP) concentrations and American College of Rheumatology (ACR) scores of 20, 50, and 70% improvement. Temporal patterns of total canakinumab, total IL-1?, CRP, and ACR scores were all well described. Simulations confirmed that 150?mg every 4 weeks improved ACR scores in patients with RA, but no additional benefit was provided by higher doses or more frequent administration. Integrating predicted endogenous free ligand concentrations with biomarkers and clinical outcomes could be extended to new therapies of anti-inflammatory diseases.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e5; doi:10.1038/psp.2012.6; advance online publication 26 September 2012.
Paolo Magni
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  • Model owner: Paolo Magni
  • Submitted: Dec 12, 2015 4:09:21 PM
  • Last Modified: Oct 13, 2016 6:30:37 PM
Revisions
  • Version: 11 public model Download this version
    • Submitted on: Oct 13, 2016 6:30:37 PM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
  • Version: 9 public model Download this version
    • Submitted on: Jul 16, 2016 4:56:30 PM
    • Submitted by: Paolo Magni
    • With comment: Updated model annotations.
  • Version: 6 public model Download this version
    • Submitted on: Dec 12, 2015 4:09:21 PM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
 
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