Using Real‐World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic‐Pharmacodynamic Study. Issue 2 (29th January 2020)

• Record Type: Journal Article
• Authors: 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.
• Other Names: Benham Marilyn investigator.; Evans Ian investigator.; Hussain Sagair investigator.; Kirby Brian investigator.; Lawson Linda investigator.; Mason Kayleigh investigator.; McElhone Kathleen investigator.; Ormerod Anthony investigator.; Owen Caroline investigator.; Barnes Michael R. investigator.; Di Meglio Paola investigator.; Emsley Richard investigator.; Evans Andrea investigator.; Payne Katherine investigator.
• Is Part Of: Clinical and translational science. Volume 13:Issue 2(2020)
• Page Start: 400
• Page End: 409
• Publication Date: 2020-01-29
• Subjects: Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; 616.027
• DOI: 10.1111/cts.12725
• Languages: English
• ISSNs: 1752-8054

Abstract

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.