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The clinical relevance of dupilumab serum concentration in patients with atopic dermatitis: a two-center prospective cohort study

Version 2 2023-05-02, 11:20
Version 1 2023-04-26, 14:21
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posted on 2023-05-02, 11:20 authored by Angela L. Bosma, Louise A. A. Gerbens, Hajar El Khattabi, Floris C. Loeff, Michael Duckworth, Richard T. Woolf, Theo Rispens, Catherine H. Smith, Phyllis I. Spuls

Dupilumab is prescribed in one dosage across adult atopic dermatitis patients. Differences in drug exposure may explain variation in treatment response.

Investigating the clinical relevance of dupilumab serum concentration in atopic dermatitis in real-world practice.

In two centers (Netherlands, UK), adults treated with dupilumab for atopic dermatitis were evaluated for effectiveness and safety pretreatment and at 2, 12, 24, and 48 weeks; trough serum samples were analyzed for dupilumab concentration at corresponding time points.

In 149 patients, median dupilumab levels during follow-up ranged from 57.4 to 72.4 μg/mL. Levels showed high inter-patient and low intra-patient variability. No correlation was found between levels and ΔEASI. At 2 weeks, levels of ≥64.1 μg/mL predict EASI ≤7 at 24 weeks (specificity:100%, sensitivity:60%; p = .022). At 12 weeks, ≤32.7 μg/mL predicts EASI >7 at 24 weeks (sensitivity:95%, specificity:26%; p = .011). Inverse correlations were found between baseline EASI and levels at 2, 12, and 24 weeks (r = −0.25 to 0.36; p ≤ .023). Low levels were particularly observed in patients with adverse events, treatment interval deviation, and discontinuation.

At the on-label dosage, the measured range of dupilumab levels does not seem to yield differences in treatment effectiveness. However, disease activity does seem to influence dupilumab levels - higher baseline disease activity results in lower levels at follow-up.

Funding

The TREAT NL registry was partly funded by a governmental grant through ZonMw (The Netherlands Organization for Health Research and Development, program Rational Pharmacotherapy), The Netherlands Pharmacovigilance Center Lareb, LEO pharma since 2019, and Novartis, Sanofi Genzyme, Pfizer and Galderma since 2020. This specific study was supported by departmental resources. National Institute for Health and Care Research (NIHR) Biomedical Research Center based at Guy’s and St Thomas ‘NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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