Association of serum ustekinumab levels with clinical response in psoriasis

Tsakok, T. et al. (2019) Association of serum ustekinumab levels with clinical response in psoriasis. JAMA Dermatology, 155(11), pp. 1235-1243. (doi: 10.1001/jamadermatol.2019.1783)

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Abstract

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.

Item Type:Articles
Additional Information:This work was funded by the Medical Research Council (MRC) Stratified Medicine award (MR/L011808/1), the Psoriasis Association (RG2/10), the National Institute for Health Research Biomedical Research Centre at King’s College London/Guy’s and St Thomas’ NHS Foundation Trust, the National Institute for Health Research Manchester Biomedical Research Centre, and the National Institute for Health Research Newcastle Biomedical Research Centre. Ms Tsakok is supported by an MRC Clinical Research Training Fellowship (MR/R001839/1). Dr Dand is supported by Health Data Research UK (MR/S003126/1). Dr Standing is supported by an MRC Clinician Scientist Fellowship (MR/M008665/1). Dr Reynolds is supported by the Newcastle MRC/EPSRC Molecular Pathology Node and the Newcastle National Institute for Health Research Medtech and In Vitro Diagnostics Co-operative.
Keywords:Dermatology.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burden, Professor David
Authors: Tsakok, T., Wilson, N., Dand, N., Loeff, F. C., Bloem, K., Baudry, D., Duckworth, M., Pan, S., Pushpa-Rajah, A., Standing, J. F., de Vries, A., Alsharqi, A., Becher, G., Murphy, R., Wahie, S., Wright, A., Griffiths, C. E. M., Reynolds, N. J., Barker, J., Warren, R. B., Burden, A. D., Rispens, T., Stocken, D., and Smith, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:JAMA Dermatology
Publisher:American Medical Association (AMA)
ISSN:2168-6068
ISSN (Online):2168-6084
Published Online:18 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in JAMA Dermatol. 2019:155(11):1235-1243
Publisher Policy:Reproduced under a Creative Commons Licence

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