Pan, S;
Tsakok, T;
Dand, N;
Lonsdale, DO;
Loeff, FC;
Bloem, K;
de Vries, A;
Baudry, D;
Duckworth, M;
Mahil, S;
et al.
Pan, S; Tsakok, T; Dand, N; Lonsdale, DO; Loeff, FC; 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, CEM; Reynolds, NJ; Barker, J; Warren, RB; David Burden, A; Rispens, T; Standing, JF; Smith, CH; BADBIR Study Group, the BSTOP Study Group, the PSORT Consortium
(2020)
Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.
Clin Transl Sci, 13 (2).
pp. 400-409.
ISSN 1752-8062
https://doi.org/10.1111/cts.12725
SGUL Authors: Lonsdale, Dagan
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.
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