Pan, S;
Tsakok, T;
Dand, N;
Lonsdale, DO;
Loeff, FC;
Bloem, K;
de Vries, A;
Baudry, D;
Duckworth, M;
Mahil, S;
et al.
Pan, S; Tsakok, T; Dand, N; Lonsdale, DO; Loeff, FC; Bloem, K; de Vries, A; Baudry, D; Duckworth, M; Mahil, S; Pushpa-Rajah, A; Russell, A; Alsharqi, A; Becher, G; Murphy, R; Wahie, S; Wright, A; Griffiths, CEM; Reynolds, NJ; Barker, J; Warren, RB; David Burden, A; Rispens, T; Standing, JF; Smith, CH; BADBIR Study Group, the BSTOP Study Group, the PSORT Consortium
(2020)
Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.
Clin Transl Sci, 13 (2).
pp. 400-409.
ISSN 1752-8062
https://doi.org/10.1111/cts.12725
SGUL Authors: Lonsdale, Dagan
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Abstract
Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes.
Item Type: | Article | ||||||||||||||||||
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Additional Information: | © 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | ||||||||||||||||||
Keywords: | General Clinical Medicine, 1102 Cardiorespiratory Medicine and Haematology, 1112 Oncology and Carcinogenesis, 1199 Other Medical and Health Sciences | ||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | Clin Transl Sci | ||||||||||||||||||
ISSN: | 1752-8062 | ||||||||||||||||||
Language: | eng | ||||||||||||||||||
Publisher License: | Creative Commons: Attribution 4.0 | ||||||||||||||||||
Projects: |
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PubMed ID: | 31995663 | ||||||||||||||||||
Web of Science ID: | WOS:000509834900001 | ||||||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/111667 | ||||||||||||||||||
Publisher's version: | https://doi.org/10.1111/cts.12725 |
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