A Pharmacodynamic Markov Mixed-Effects Model for Determining the Effect of Exposure to Certolizumab Pegol on the ACR20 Score in Patients With Rheumatoid Arthritis
2009 (English)In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6519, Vol. 86, no 4, 387-395 p.Article in journal, News item (Refereed) Published
The American College of Rheumatology 20% preliminary definition of improvement of rheumatoid arthritis (ACR20) is widely used in clinical trials to assess response to treatment. The objective of this analysis was to develop an exposure-response model of ACR20 in subjects treated with certolizumab pegol, and to predict clinical outcome following various treatment schedules. At each visit, subjects were classified as being ACR20 responders, ACR20 non-responders, or having dropped out. A Markov mixed-effect model was developed to investigate the drug effect on the transitions between the 3 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. Simulations of the ACR20 response rate support dosing regimens of 400 mg at weeks 0, 2 and 4 followed by 200 mg every 2 weeks, or alternative maintenance regimen of 400 mg every 4 weeks.
Place, publisher, year, edition, pages
Nature Publishing Group, 2009. Vol. 86, no 4, 387-395 p.
Rheumatoid arthritis, ACR20, exposure-response modeling, Markov, certolizumab pegol
Pharmaceutical Sciences Pharmacology and Toxicology
Research subject Clinical Pharmacology; Pharmacokinetics and Drug Therapy
IdentifiersURN: urn:nbn:se:uu:diva-247890DOI: 10.1038/clpt.2009.136OAI: oai:DiVA.org:uu-247890DiVA: diva2:797893