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

被引:13
|
作者
Bachert, Claus [1 ,2 ,3 ,16 ]
Laidlaw, Tanya M. [4 ]
Cho, Seong H. [5 ]
Mullol, Joaquim [6 ]
Swanson, Brian N. [7 ,8 ]
Naimi, Souad [9 ]
Classe, Marion [10 ,11 ]
Harel, Sivan [12 ]
Jagerschmidt, Alexandre [13 ]
Laws, Elizabeth [14 ]
Ruddy, Marcella [12 ]
Praestgaard, Amy [15 ]
Amin, Nikhil [12 ]
Mannent, Leda P. [13 ]
机构
[1] Univ Hosp Munster, Dept Otorhinolaryngol Head & Neck Surg, Munster, Germany
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Int Airway Res Ctr, Guangzhou, Peoples R China
[3] Univ Ghent, Fac Med, Upper Airways Res Lab, Ghent, Belgium
[4] Harvard Med Sch, Brigham & Womens Hosp, Div Allergy & Clin Immunol, Boston, MA USA
[5] Univ S Florida, Morsani Coll Med, Div Allergy Immunol, Tampa, FL USA
[6] Univ Barcelona, Hosp Clin, ENT Dept, Rhinol Unit & Smell Clin,IDIBAPS,CIBERES, Barcelona, Catalonia, Spain
[7] Thomas Jefferson Univ, Coll Life Sci, Philadelphia, PA USA
[8] Sanofi, Res & Dev, Bridgewater, NJ USA
[9] Sanofi, Mol & Digital Histopathol, Vitry Sur Seine, France
[10] Inst Gustave Roussy, Pathol Dept, Villejuif, France
[11] Sanofi, Translat Sci, Chilly Mazarin, France
[12] Regeneron Pharmaceut Inc, Clin Sci Global Dev, Tarrytown, NY USA
[13] Sanofi, Global Clin Dev, Chilly Mazarin, France
[14] Sanofi, Immunol & Inflammat Global Dev, Bridgewater, NJ USA
[15] Sanofi, Dept Biostat, Cambridge, MA USA
[16] Univ Hosp Munster, Dept Otorhinolaryngol Head & Neck Surg, Kardinal Von Galen Ring 10, D-48149 Munster, Germany
来源
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY | 2023年
关键词
asthma; biomarkers; comorbidities; CRSwNP; dupilumab; NSAID-ERD; type; 2; inflammation; ASTHMA; IGE; PREVALENCE; ANTIBODIES; CYTOKINES; ALLERGY; PROTEIN;
D O I
10.1177/00034894231176334
中图分类号
R76 [耳鼻咽喉科学];
学科分类号
100213 ;
摘要
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-4 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-4 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.ClinicalTrials.gov Identifier:NCT02898454
引用
收藏
页码:1649 / 1661
页数:13
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