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Simultaneous Exposure-Response Modeling of ACR20, ACR50, and ACR70 Improvement
Scores in Rheumatoid Arthritis Patients Treated With Certolizumab Pegol
#MMPMID25353186
Lacroix BD
; Karlsson MO
; Friberg LE
CPT Pharmacometrics Syst Pharmacol
2014[Oct]; 3
(10
): e143
PMID25353186
show ga
The Markovian approach has been proposed to model American College of
Rheumatology's (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 three thresholds: a
continuous-time Markov exposure-response model was developed, based on data from
five 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 (50-400?mg every other week) illustrated the range and
sustainability of response (ACR20: 56-68%, ACR50: 27-42%, ACR70: 11-22% at week
24) with maximum clinical effect achieved at the recommended maintenance dose of
200?mg every other week.
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