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

BADBIR Study Group, the BSTOP Study Group, the PSORT Consortium, Shan Pan, Teresa Tsakok, Nick Dand, Dagan O Lonsdale, Floris C Loeff, Karien Bloem, Annick de Vries, David Baudry, Michael Duckworth, Satveer Mahil, Angela Pushpa-Rajah, Alice Russell, Ali Alsharqi, Gabrielle Becher, Ruth Murphy, Shyamal Wahie, Andrew Wright, Christopher E M Griffiths, Nick J ReynoldsJonathan Barker, Richard B Warren, A David Burden, Theo Rispens, Joseph F Standing, Catherine H Smith

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)400-409
Number of pages10
JournalClinical and Translational Science
Volume13
Issue number2
Early online date29 Jan 2020
DOIs
Publication statusPublished - 1 Mar 2020

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