| Title: |
Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study. |
| Authors: |
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 |
| Publisher Information: |
Wiley |
| Publication Year: |
2020 |
| Collection: |
St George's University of London: Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1752-8062 |
| Relation: |
https://openaccess.sgul.ac.uk/id/eprint/111667/1/Pan_et_al-2020-Clinical_and_Translational_Science.pdf; 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 |
| Availability: |
https://openaccess.sgul.ac.uk/id/eprint/111667/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.A92B0091 |
| Database: |
BASE |