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Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study

Lookup NU author(s): Dr Shyamal Wahie, Professor Nick Reynolds

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Abstract

© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. 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.


Publication metadata

Author(s): 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, Benham M, Evans I, Hussain S, Kirby B, Lawson L, Mason K, McElhone K, Ormerod A, Owen C, Barnes MR, Di Meglio P, Emsley R, Evans A, Payne K

Publication type: Article

Publication status: Published

Journal: Clinical and Translational Science

Year: 2020

Volume: 13

Issue: 2

Pages: 400-409

Print publication date: 01/03/2020

Online publication date: 29/01/2020

Acceptance date: 14/10/2019

Date deposited: 10/02/2020

ISSN (print): 1752-8054

ISSN (electronic): 1752-8062

Publisher: Wiley Periodicals, Inc.

URL: https://doi.org/10.1111/cts.12725

DOI: 10.1111/cts.12725


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