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Randomized Controlled Trial
. 2011 Apr;38(2):237-60.
doi: 10.1007/s10928-011-9191-7. Epub 2011 Feb 13.

Informative dropout modeling of longitudinal ordered categorical data and model validation: application to exposure-response modeling of physician's global assessment score for ustekinumab in patients with psoriasis

Chuanpu Hu  1 , Philippe O Szapary, Newman Yeilding, Honghui Zhou
Affiliations
Randomized Controlled Trial

Informative dropout modeling of longitudinal ordered categorical data and model validation: application to exposure-response modeling of physician's global assessment score for ustekinumab in patients with psoriasis

Chuanpu Hu et al. J Pharmacokinet Pharmacodyn. 2011 Apr.

Abstract

The physician's global assessment (PGA) score is a 6-point measure of psoriasis severity that is widely used in clinical trials to assess response to psoriasis treatment. The objective of this study was to perform exposure-response modeling using the PGA score as a pharmacodynamic endpoint following treatment with ustekinumab in patients with moderate-to-severe psoriasis who participated in two Phase 3 studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 or 90 mg or placebo, followed by active treatment or placebo crossover to ustekinumab, dose intensification or randomized withdrawal and long-term extension periods. A novel joint longitudinal-dropout model was developed from serum ustekinumab concentrations, PGA scores, and patient dropout information. The exposure-response component employed a semi-mechanistic drug model, integrated with disease progression and placebo effect under the mixed-effect logistic regression framework. This allowed potential tolerance to be investigated with a mechanistic approach. The dropout component of the joint model allowed the examination of its potential influence on the exposure-response relationship. The flexible Weibull dropout hazard function was used. Visual predictive check of the joint longitudinal-dropout model required special handling, and a conditional approach was proposed. The conditional approach was extended to external model validation. Finally, appropriate interpretation of model validation is discussed. This longitudinal-dropout model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate-to-severe plaque psoriasis.

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References

    1. Clin Pharmacol Ther. 1994 Sep;56(3):309-22 - PubMed
    1. J Exp Med. 2006 Nov 27;203(12):2577-87 - PubMed
    1. J Pharmacokinet Pharmacodyn. 2008 Feb;35(1):101-16 - PubMed
    1. J Clin Pharmacol. 2010 Mar;50(3):257-67 - PubMed
    1. J Pharmacokinet Pharmacodyn. 2003 Dec;30(6):387-404 - PubMed

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