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

Abstract

Background

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

Objective

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

Methods

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.

Results

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.

Conclusion

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.

Keywords:

• Atopic dermatitis
• dupilumab
• serum concentration

Acknowledgments

The authors would like to thank Ariënna Hyseni and Bryan van den Broek for their assistance.

Disclosure statement

RW: Principal or co-investigator in clinical trials – Abbvie, Amgen, Anaptys Bio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen-Cilag, Kymab, Leo Pharma, Pfizer, Sanofi and UCB. Honoraria from and consultancy work for Abbvie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, Sandoz, Sanofi and UCB. Honoraria from NICE (clinical expert).

PS: receives departmental independent research grants for TREAT NL registry, for which she is Chief Investigator (CI), from pharma companies since December 2019, is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g., psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital.

AB, CS and PS: Investigators on IMI-EU funded research consortium to identify biomarkers in atopic dermatitis; multiple industry partners including Sanofi (biomap-imi.eu). All financial compensation is paid to the department/hospital.

No other conflicts of interest were reported.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Additional information

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.