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

Pan, Shan; Tsakok, Teresa; Dand, Nick; Lonsdale, Dagan O.; Loeff, Floris C.; Bloem, Karien; de Vries, Annick; Baudry, David; Duckworth, Michael; Mahil, Satveer; Pushpa-Rajah, Angela; Russell, Alice; Alsharqi, Ali; Becher, Gabrielle; Murphy, Ruth; Wahie, Shyamal; Wright, Andrew; Griffiths, Christopher E.M.; Reynolds, Nick J.; Barker, Jonathan; Warren, Richard B.; David Burden, A.; Rispens, Theo; Standing, Joseph F.; Smith, Catherine H.; Study Group, BADBIR; Benham, Marilyn; Evans, Ian; Hussain, Sagair; Kirby, Brian; Lawson, Linda; Mason, Kayleigh; McElhone, Kathleen; Ormerod, Anthony; Owen, Caroline; Consortium, PSORT; Barnes, Michael R.; Di Meglio, Paola; Emsley, Richard; Evans, Andrea; Payne, Katherine; Study Group, BSTOP

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Authors

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. Reynolds

Jonathan Barker

Richard B. Warren

A. David Burden

Theo Rispens

Joseph F. Standing

Catherine H. Smith

BADBIR Study Group

Marilyn Benham

Ian Evans

Sagair Hussain

Brian Kirby

Linda Lawson

Kayleigh Mason

Kathleen McElhone

Anthony Ormerod

Caroline Owen

PSORT Consortium

Michael R. Barnes

Paola Di Meglio

Richard Emsley

Andrea Evans

Katherine Payne

BSTOP Study Group



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.

Journal Article Type Article
Acceptance Date Oct 14, 2020
Online Publication Date Jan 29, 2020
Publication Date 2020-03
Journal Clinical and Translational Science
Print ISSN 1752-8054
Publisher Wiley Open Access
Peer Reviewed Peer Reviewed
Volume 13
Issue 2
Pages 400 - 409
DOI https://doi.org/10.1111/cts.12725
Publisher URL https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.12725

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