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Cited by 192Dermatology and Skin DiseasesAsthma and respiratory diseasesAllergic Rhinitis and Sensitization

Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases

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Hamilton, Jennifer D., Harel, Sivan, Swanson, Brian N., Brian, William, Chen, Zhen, Rice, Megan S., Amin, Nikhil, Ardeleanu, Marius +7 more·2021·Clinical & Experimental Allergy
DOI 10.1111/cea.13954PMC PMC8362102
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Abstract

BACKGROUND: Type 2 inflammation is common in numerous atopic/allergic diseases and can be identified by elevated biomarker levels. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. OBJECTIVE: Assessment of dupilumab effect on type 2 inflammatory biomarkers in atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE). METHODS: Data were extracted from three randomized placebo-controlled trials of dupilumab in AD (NCT02277743, N = 671; NCT02277769, N = 708; NCT02260986, N = 740); and one each in asthma (NCT02414854, N = 1902); CRSwNP (NCT02898454, N = 448); and EoE (NCT02379052, N = 47). Biomarkers assessed were serum thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, serum total immunoglobulin E (IgE), serum periostin and blood eosinophil count. RESULTS: Dupilumab versus placebo significantly suppressed most type 2 inflammatory biomarker levels across all studies/indications where data were assessed. Reductions in serum TARC, plasma eotaxin-3 and serum periostin occurred rapidly, whereas reductions in serum total IgE were more gradual. Across diseases, at the end of treatment, median percentage change from baseline in TARC levels ranged from -24.8% to -88.6% (placebo +2.6% to -53.6%); -38.2% to -51.5% (placebo +8.3% to -0.16%) in eotaxin-3; -24.8% to -76.7% (placebo +8.3% to -4.4%) in total IgE; and -13.6% to -41.1% (placebo +10.1% to -6.94%) in periostin levels. Blood eosinophil responses to dupilumab varied by disease, with minimal changes in AD in the SOLO studies (median percentage change from baseline to end of treatment: 0% [95% CI: -15.8, 0]); transient increases followed by decreases to below-baseline levels in asthma (-14.6% [-20.0, -7.7]) and CRSwNP (-29.4% [-40.0, -16.3]); and significant decreases in EoE (-50.0% [-50.0, -33.3]). CONCLUSION AND CLINICAL RELEVANCE: Dupilumab reduced levels of type 2 biomarkers across clinical studies in patients with AD, asthma, CRSwNP and EoE.

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  • The current model does not yet capture inter-patient variability in pharmacological responses or the full chronicity of clinical AD.

    “These pharmacological responses are mechanistically consistent with the known mechanisms of these therapeutics, whereas the current model does not yet capture inter-patient variability in pharmacological responses or the full chronicity of clinical AD [46][47][48] .”

    From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [46]

    The Methods (Studies and patients) describe clinical dupilumab trials, and the Results (Serum TARC) mention a statistical ANCOVA model. Neither passage addresses whether the citing authors’ current model captures inter-patient variability in drug responses or the chronicity of clinical AD. Searches for those model limitations found no relevant passage in our copy; page numbers were not provided. (LLM, conf=0.75)

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Cited by

Sorted by citations

Authors
Hamilton, J. D., Harel, S., Swanson, B. N., Brian, W., Chen, Z., Rice, M. S., Amin, N., Ardeleanu, M., Radin, A., Shumel, B., Ruddy, M., Patel, N., Pirozzi, G., Mannent, L., & Graham, N. M. H.
Affiliations
  • Regeneron (United States) (US)
  • Sanofi (United States) (US)
  • Sanofi Cambridge MA USA
  • Sanofi (France) (FR)
Corresponding author
Hamilton, Jennifer D.
ORCID
Venue
Clinical & Experimental Allergy
Publisher
Wiley
Published
2021-06-26
Volume
51
Issue
7
Pages
915-931
ISSN
  • 0954-7894 (ISSN-L)
  • 1365-2222
DOI
10.1111/cea.13954
PMC
PMC8362102
OpenAlex
W3163989045
Cited by
192
References
2
Citations by year
2026: 28 · 2025: 46 · 2024: 41 · 2023: 37 · 2022: 33 · 2021: 5
FWCI
25.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical & Experimental Allergy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Sanofi
  • Regeneron Pharmaceuticals
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
Keywords
umab, type 2 inflammation, atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, IL-4 receptor alpha, CCL17, eotaxin-3, periostin, total IgE, blood eosinophils, biomarkers
MeSH terms
Chemokine CCL26, Eosinophils, Humans, Hypersensitivity, Immediate, Immunoglobulin E, Inflammation, Biomarkers, Cell Adhesion Molecules, Randomized Controlled Trials as Topic, Chemokine CCL17, Antibodies, Monoclonal, Humanized

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