Dupilumab reduces local type 2 pro‐inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis. Issue 4 (21st January 2019)

• Record Type: Journal Article
• Authors: Jonstam, Karin; Swanson, Brian N.; Mannent, Leda P.; Cardell, Lars‐Olaf; Tian, Nian; Wang, Ying; Zhang, Donghui; Fan, Chunpeng; Holtappels, Gabriele; Hamilton, Jennifer D.; Grabher, Annette; Graham, Neil M. H.; Pirozzi, Gianluca; Bachert, Claus
• Is Part Of: Allergy. Volume 74:Issue 4(2019)
• Page Start: 743
• Page End: 752
• Publication Date: 2019-01-21
• Subjects: biomarkers -- dupilumab -- nasal polyposis -- nasal secretions -- type 2 inflammation; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.13685
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: 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. Abstract : Dupilumab reduced multiple type 2 inflammation biomarkers in nasal secretions and polyp tissues of patients with chronic rhinosinusitis with nasal polyposis, including total IgE and chemoattractants for inflammatory cells Local reductions in type 2 biomarkers were consistent with overall, parallel improvements in nasosinal symptoms and reductions in polypoid tissue These findings suggest that inhibition of IL‐4/IL‐13 signaling via dupilumab‐mediated blockade of IL‐4Rα can suppress underlying inflammation of nasal polyposis, leading to clinical benefits