TY - JOUR
T1 - Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis
T2 - A Prospective Pharmacokinetic-Pharmacodynamic Study
AU - BADBIR Study Group, the BSTOP Study Group, the PSORT Consortium
AU - Pan, Shan
AU - Tsakok, Teresa
AU - Dand, Nick
AU - Lonsdale, Dagan O
AU - Loeff, Floris C
AU - Bloem, Karien
AU - de Vries, Annick
AU - Baudry, David
AU - Duckworth, Michael
AU - Mahil, Satveer
AU - Pushpa-Rajah, Angela
AU - Russell, Alice
AU - Alsharqi, Ali
AU - Becher, Gabrielle
AU - Murphy, Ruth
AU - Wahie, Shyamal
AU - Wright, Andrew
AU - Griffiths, Christopher E M
AU - Reynolds, Nick J
AU - Barker, Jonathan
AU - Warren, Richard B
AU - David Burden, A
AU - Rispens, Theo
AU - Standing, Joseph F
AU - Smith, Catherine H
N1 - © 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85078663993&partnerID=8YFLogxK
U2 - 10.1111/cts.12725
DO - 10.1111/cts.12725
M3 - Article
C2 - 31995663
VL - 13
SP - 400
EP - 409
JO - Clinical and Translational Science
JF - Clinical and Translational Science
IS - 2
ER -