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Clin Transl Sci. 2020 Jan 29. doi: 10.1111/cts.12725. [Epub ahead of print]

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

Author information

1
St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
2
St. John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
3
Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
4
Institute of Infection and Immunity, St. George's, University of London, London, UK.
5
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
6
Biologics Lab, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
7
Dermatology Department, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, UK.
8
West Glasgow Ambulatory Care Hospital, Glasgow, UK.
9
Department of Dermatology, Queens Medical Centre, Nottingham University Teaching Hospitals, Nottingham, UK.
10
Dermatology Department, University Hospital of North Durham, Durham, UK.
11
Centre for Skin Sciences, University of Bradford, Bradford, UK.
12
Dermatology Centre, Salford Royal National Health Service Foundation Trust, Manchester, UK.
13
The University of Manchester, Manchester Academic Health Science Centre, National Institute for Health Research Manchester Biomedical Research Centre, Manchester, UK.
14
Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
15
Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
16
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
17
Infection, Immunity, Inflammation Section, UCL Great Ormond Street Institute of Child Health, London, UK.

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.

PMID:
31995663
DOI:
10.1111/cts.12725

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