Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis.
Allergy
; 74(4): 743-752, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-30488542
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinusitis
/
Rinitis
/
Pólipos Nasales
/
Anticuerpos Monoclonales Humanizados
/
Inflamación
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Allergy
Año:
2019
Tipo del documento:
Article
País de afiliación:
Suecia