Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study

Autor: 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., David Burden, A., 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., Payne, K.
Přispěvatelé: Landsteiner Laboratory, AII - Inflammatory diseases
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Oncology
Male
030226 pharmacology & pharmacy
Severity of Illness Index
030207 dermatology & venereal diseases
0302 clinical medicine
Drug Dosage Calculations
Prospective Studies
General Pharmacology
Toxicology and Pharmaceutics
Prospective cohort study
media_common
medicine.diagnostic_test
General Neuroscience
lcsh:Public aspects of medicine
R735
General Medicine
Articles
Middle Aged
3. Good health
Treatment Outcome
Female
Ustekinumab
Drug Monitoring
medicine.drug
Drug
Adult
medicine.medical_specialty
RM
Adolescent
media_common.quotation_subject
Injections
Subcutaneous
RL
Models
Biological
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Young Adult
Pharmacokinetics
Psoriasis
Internal medicine
medicine
Humans
Dosing
Aged
business.industry
Research
lcsh:RM1-950
Bayes Theorem
lcsh:RA1-1270
medicine.disease
R1
lcsh:Therapeutics. Pharmacology
Therapeutic drug monitoring
Pharmacodynamics
Dermatologic Agents
business
Zdroj: CTS-CLINICAL AND TRANSLATIONAL SCIENCE, 13(2), 400-409. Wiley-Blackwell
Clinical and Translational Science, Vol 13, Iss 2, Pp 400-409 (2020)
Clinical and Translational Science
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, David Burden, A, Rispens, T & Standing, J F & Smith, C H 2020, ' Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis : A Prospective Pharmacokinetic-Pharmacodynamic Study ', Clinical and Translational Science, vol. 13, no. 2, pp. 400-409 . https://doi.org/10.1111/cts.12725, https://doi.org/10.1111/cts.12725
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, David Burden, A, 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 & Payne, K 2020, ' Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study ', Clinical and Translational Science, vol. 13, no. 2, pp. 400-409 . https://doi.org/10.1111/cts.12725
ISSN: 1752-8054
1752-8062
Popis: 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 (E max) 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.
Databáze: OpenAIRE
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