Using real‐world data to guide ustekinumab dosing strategies for psoriasis: a prospective pharmacokinetic‐pharmacodynamic study

Pan, S. et al. (2020) Using real‐world data to guide ustekinumab dosing strategies for psoriasis: a prospective pharmacokinetic‐pharmacodynamic study. Clinical and Translational Science, 13(2), pp. 400-409. (doi: 10.1111/cts.12725) (PMID:31995663) (PMCID:PMC7070790)

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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:Articles
Additional Information:This work was funded by a Medical Research Council (MRC) Stratified Medicine award (MR/L011808/1). The Psoriasis Association (RG2/10), the NIHR Biomedical Research Centre at King’s College London/ Guy’s and St. Thomas’ NHS Foundation Trust, the NIHR Manchester Biomedical Research Centre, and the NIHR Newcastle Biomedical Research Centre. T.T. is supported by an MRC Clinical Research Training Fellowship (MR/R001839/1). N.D. is supported by Health Data Research UK (MR/ S003126/1). N.J.R. is supported by the Newcastle MRC/EPSRC Molecular Pathology Node and the Newcastle NIHR Medtech and In vitro diagnostics Co-operative. C.E.M.G. and N.J.R. are NIHR Senior Investigators. J.F.S. is supported by an MRC Fellowship (MR/M008665/1).
Keywords:General Pharmacology, Toxicology and Pharmaceutics, General Biochemistry, Genetics and Molecular Biology, General Neuroscience, General Medicine
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burden, Professor David
Authors: Pan, S., Tsakok, T., Dand, N., Lonsdale, D. O., Loeff, F. C., 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, C. E.M., Reynolds, N. J., Barker, J., Warren, R. B., Burden, A. D., Rispens, T., Standing, J. F., Smith, C. H., Benham, M., Evans, I., Hussain, S., Kirby, B., Lawson, L., Mason, K., McElhone, K., Ormerod, A., Owen, C., Barnes, M. R., Di Meglio, P., Emsley, R., Evans, A., and Payne, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Clinical and Translational Science
Publisher:Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
ISSN:1752-8054
ISSN (Online):1752-8062
Published Online:29 January 2020
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Clinical and Translational Science
Publisher Policy:Reproduced under a Creative Commons Licence

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