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Dupilumab reduces local type 2 pro‐inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis
Author(s) -
Jonstam Karin,
Swanson Brian N.,
Mannent Leda P.,
Cardell LarsOlaf,
Tian Nian,
Wang Ying,
Zhang Donghui,
Fan Chunpeng,
Holtappels Gabriele,
Hamilton Jennifer D.,
Grabher Annette,
Graham Neil M. H.,
Pirozzi Gianluca,
Bachert Claus
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13685
Subject(s) - dupilumab , medicine , nasal polyps , immunology , immunoglobulin e , eotaxin , sinusitis , biomarker , placebo , gastroenterology , asthma , eosinophil , antibody , pathology , biochemistry , chemistry , alternative medicine
Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2‐mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin‐4 receptor α (IL‐4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo‐controlled, phase 2 trial (NCT01920893). Methods Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks. Results With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin‐3 (−30.06 vs −0.86 pg/mL; P = 0.0008) and total IgE (−7.90 vs −1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein ( P = 0.008), eotaxin‐2 ( P = 0.008), eotaxin‐3 ( P = 0.031), pulmonary and activation‐regulated chemokine ( P = 0.016), IgE ( P = 0.023), and IL‐13 ( P = 0.031). Conclusions Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL‐4Rα signaling suppresses IL‐4‐/IL‐13‐dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.