DDMODEL00000109: Lacroix_2009_Markov model

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Short description:
A mixed-effects Markov model was developed to describe the probability of ACR20 response (20% improvement in the American College of Rheumatology criteria) as a function of certolizumab pegol exposure, rheumatoid arthritis disease, and placebo response. A model based on the data from placebo-treated subjects was first developed. The structural first-order Markov model described the time course of the transition probabilities between non-responder, responder, and dropout states (i.e., the probabilities for subjects being in each of the three defined states at each study visit conditioned on their state at the previous visit).
Original code
  • A pharmacodynamic Markov mixed-effects model for determining the effect of exposure to certolizumab pegol on the ACR20 score in patients with rheumatoid arthritis.
  • Lacroix BD, Lovern MR, Stockis A, Sargentini-Maier ML, Karlsson MO, Friberg LE
  • Clinical pharmacology and therapeutics, 10/2009, Volume 86, Issue 4, pages: 387-395
  • Pharmacometrics, Department of Global Exploratory Development, UCB Pharma SA, Braine-l'Alleud, Belgium. brigitte.lacroix@ucb.com
  • The American College of Rheumatology (ACR) 20% preliminary definition of improvement in rheumatoid arthritis (RA) (ACR20) is widely used in clinical trials to assess response to treatment. The objectives of this analysis were to develop an exposure-response model of ACR20 in subjects receiving treatment with certolizumab pegol and to predict clinical outcomes following various treatment schedules. At each visit, subjects were classified as being ACR20 responders or ACR20 nonresponders or as having dropped out. A Markov mixed-effects model was developed to investigate the effects of the drug on the transitions between the three defined states. Increasing certolizumab pegol exposure predicted an increasing probability of becoming a responder and remaining a responder, as well as a reduced probability of dropping out of treatment. Data from simulations of the ACR20 response rate support the use of dosing regimens of 400 mg at weeks 0, 2, and 4 followed by 200 mg every 2 weeks, or an alternative maintenance regimen of 400 mg every 4 weeks.
Roberto Gomeni
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  • Model owner: Roberto Gomeni
  • Submitted: Dec 15, 2015 3:33:51 PM
  • Last Modified: Dec 15, 2015 3:33:51 PM
  • Version: 12 public model Download this version
    • Submitted on: Dec 15, 2015 3:33:51 PM
    • Submitted by: Roberto Gomeni
    • With comment: Edited model metadata online.