Simultaneous Exposure-Response Modeling of ACR20, ACR50, and ACR70 Improvement Scores in Rheumatoid Arthritis Patients With Certolizumab Pegol
2014 (English)In: CPT Pharmacometrics and Systems Pharmacology, ISSN 2163-8306, Vol. 3, no 10, 1-11 p.Article in journal (Refereed) Published
The Markovian approach has been proposed to model ACR response (ACR20, ACR50 or ACR70) reported in rheumatoid arthritis clinical trials to account for the dependency of the scores over time. However, dichotomizing the composite ACR assessment discards much information. Here we propose a new approach for modeling together the 3 thresholds: a continuous-time Markov exposure-response model was developed, based on data from 5 placebo-controlled certolizumab pegol clinical trials. This approach allows adequate prediction of individual ACR20/50/70 time-response, even for non-periodic observations. An exposure-response was established over a large range of licensed and unlicensed doses including phase II dose-ranging data. Simulations from the model (50 to 400 mg every other week) illustrated the range and sustainability of response (ACR20: 56 to 68%, ACR50: 27 to 42%, ACR70: 11 to 22% at week 24) with maximum clinical effect achieved at the recommended maintenance dose of 200 mg every other week.
Place, publisher, year, edition, pages
Nature Publishing Group, 2014. Vol. 3, no 10, 1-11 p.
Rheumatoid arthritis, ACR, ACR20, ACR50, ACR70, exposure-response modeling, Markov, certolizumab pegol
Research subject Pharmacokinetics and Drug Therapy; Pharmaceutical Science; Pharmacology
IdentifiersURN: urn:nbn:se:uu:diva-247891DOI: 10.1038/psp.2014.41OAI: oai:DiVA.org:uu-247891DiVA: diva2:797898