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Effect of Dupilumab on Type 2 Biomarkers in Chronic Rhinosinusitis With Nasal Polyps: SINUS-52 Study Results.

Authors :
Bachert, Claus
Laidlaw, Tanya M.
Cho, Seong H.
Mullol, Joaquim
Swanson, Brian N.
Naimi, Souad
Classe, Marion
Harel, Sivan
Jagerschmidt, Alexandre
Laws, Elizabeth
Ruddy, Marcella
Praestgaard, Amy
Amin, Nikhil
Mannent, Leda P.
Source :
Annals of Otology, Rhinology & Laryngology; Dec2023, Vol. 132 Issue 12, p1649-1661, 13p
Publication Year :
2023

Abstract

Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) are frequent coexisting conditions and share type 2 inflammatory pathophysiology, with interleukin (IL)-4 and IL-13 as key cytokines. Dupilumab is a monoclonal antibody that blocks the shared receptor for IL-4 and IL-13. The objective of this analysis was to evaluate dupilumab's effect on type 2 inflammation biomarkers in patients with CRSwNP with/without coexisting asthma or NSAID-ERD from the SINUS-52 (NCT02898454) study. Methods: Patients received treatment with dupilumab or placebo for 52 weeks. Blood and urinary biomarkers were evaluated through 52 weeks, and nasal secretions and mucosa brushings through 24 weeks. Results: Of 447 patients, 60% had coexisting asthma and 27% had coexisting NSAID-ERD. At baseline, blood eotaxin-3, eosinophils, and periostin, nasal secretion eotaxin-3, and urinary leukotriene E<subscript>4</subscript> were significantly higher in patients with coexisting NSAID-ERD than without. Dupilumab reduced eotaxin-3, thymus and activation-regulated chemokine, periostin, and total immunoglobulin E in blood, eotaxin-3, periostin, IL-5, and eosinophil cationic protein in nasal secretions, and leukotriene E<subscript>4</subscript> in urine. Reductions were generally similar or greater in the subgroups with asthma and NSAID-ERD than without. Dupilumab also reduced MUC5AC and mast cell counts in nasal mucosa brushings. Conclusion: Dupilumab reduced local and systemic type 2 inflammatory biomarkers in patients with CRSwNP, including mast cells in nasal mucosa and cysteinyl leukotrienes in urine. These findings provide insight into the processes driving CRSwNP and the mechanisms of dupilumab's therapeutic effects. Clinical Trial Registry Name: SINUS-52 https://www.clinicaltrials.gov/ct2/show/NCT02898454 ClinicalTrials.gov Identifier: NCT02898454 [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00034894
Volume :
132
Issue :
12
Database :
Complementary Index
Journal :
Annals of Otology, Rhinology & Laryngology
Publication Type :
Academic Journal
Accession number :
172986774
Full Text :
https://doi.org/10.1177/00034894231176334