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Defining the therapeutic range for adalimumab and predicting response in psoriasis: amulticenter prospective observational cohort study

Lookup NU author(s): Dr Nina WilsonORCiD, Professor Nick ReynoldsORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Biologics have transformed management of inflammatory diseases. To optimize outcomesand reduce costs, dose adjustment informed by circulating drug levels has been proposed. Weaimed to determine the real-world clinical utility of therapeutic drug monitoring in psoriasis.Within a multicenter (n=60) prospective observational cohort, 544 psoriasis patients wereincluded who were on adalimumab monotherapy, with at least one serum sample and PASI(Psoriasis Area and Severity Index) score available within the first year. We present modelsgiving individualized probabilities of response for any given drug level: a minimally effectivedrug level of 3.2 μg/ml discriminates responders (PASI75: 75% improvement in baselinePASI) from non-responders and gives an estimated PASI75 probability of 65% (95% CI 60-71%). At 7ug/ml, PASI75 probability is 81% (95% CI 76-86%); beyond 7ug/ml, the druglevel/response curve plateaus. Crucially, drug levels are predictive of response 6 monthslater, whether sampled early or at steady state. We confirm serum drug level to be the mostimportant factor determining treatment response, highlighting the need to take drug levelsinto account when searching for biomarkers of response.This real-world study with pragmatic drug level sampling provides evidence to support theproactive measurement of adalimumab levels in psoriasis to direct treatment strategy, and isrelevant to other inflammatory diseases.


Publication metadata

Author(s): Wilkinson N, Tsakok T, Dand N, Bloem K, Duckworth M, Baudry D, Pushpa-Rajah A, Griffiths CEM, Reynolds N, Barker J, Warren RB, Burden AD, Rispens T, Stocken D, Smith C, BSTOP study group, PSORT consortium

Publication type: Article

Publication status: Published

Journal: Journal of Investigative Dermatology

Year: 2019

Volume: 139

Issue: 1

Pages: 115-123

Print publication date: 01/01/2019

Online publication date: 18/08/2018

Acceptance date: 15/07/2018

Date deposited: 10/10/2018

ISSN (print): 0022-202X

ISSN (electronic): 1523-1747

Publisher: Nature Publishing Group

URL: https://doi.org/10.1016/j.jid.2018.07.028

DOI: 10.1016/j.jid.2018.07.028


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Funding

Funder referenceFunder name
MR/L011808/1
MR/R001839/1
MRC/ESPRC Molecular Pathology Node
Newcastle NIHR Medtech and In vitro diagnostics Co-operative
RG2/10

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