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Lookup NU author(s): Dr Nina WilsonORCiD, Professor Nick ReynoldsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. Design, Setting, and Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). Conclusions and Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome..
Author(s): Tsakok T, Wilson N, Dand N, Loeff FC, Bloem K, Baudry D, Duckworth M, Pan S, Pushpa-Rajah A, Standing JF, De Vries A, Alsharqi A, Becher G, Murphy R, Wahie S, Wright A, Griffiths CEM, Reynolds NJ, Barker J, Warren RB, Burden AD, Rispens T, Stocken D, Smith C
Publication type: Article
Publication status: Published
Journal: JAMA Dermatology
Year: 2019
Volume: 155
Issue: 11
Pages: 1235-1243
Online publication date: 18/09/2019
Acceptance date: 30/04/2019
Date deposited: 02/10/2019
ISSN (print): 2168-6068
ISSN (electronic): 2168-6084
Publisher: American Medical Association
URL: https://doi.org/10.1001/jamadermatol.2019.1783
DOI: 10.1001/jamadermatol.2019.1783
PubMed id: 31532460
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