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

Authors :
Hamilton, Jennifer D.
Harel, Sivan
Swanson, Brian N.
Brian, William
Chen, Zhen
Rice, Megan S.
Amin, Nikhil
Ardeleanu, Marius
Radin, Allen
Shumel, Brad
Ruddy, Marcella
Patel, Naimish
Pirozzi, Gianluca
Mannent, Leda
Graham, Neil M. H.
Source :
Clinical & Experimental Allergy. Jul2021, Vol. 51 Issue 7, p915-931. 17p. 2 Diagrams, 2 Charts, 5 Graphs.
Publication Year :
2021

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09547894
Volume :
51
Issue :
7
Database :
Academic Search Index
Journal :
Clinical & Experimental Allergy
Publication Type :
Academic Journal
Accession number :
151133758
Full Text :
https://doi.org/10.1111/cea.13954