Olfactory Outcomes With Dupilumab in Chronic Rhinosinusitis With Nasal Polyps.


Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
04 2022
Historique:
received: 12 05 2021
revised: 15 09 2021
accepted: 21 09 2021
pubmed: 11 10 2021
medline: 13 4 2022
entrez: 10 10 2021
Statut: ppublish

Résumé

Loss of smell (LoS) is one of the most troublesome and difficult-to-treat symptoms of severe chronic rhinosinusitis with nasal polyps (CRSwNP). To assess the impact of dupilumab on sense of smell in severe CRSwNP. In the randomized SINUS-24 and SINUS-52 studies, adults with severe CRSwNP received dupilumab 300 mg subcutaneously or matching placebo every 2 weeks for 24 or 52 weeks, respectively. Smell was assessed using daily patient-reported LoS score (0-3) and University of Pennsylvania Smell Identification Test (UPSIT; 0-40). Data from the 2 studies were pooled through week 24. Relationships between patient phenotypes and smell outcomes were also assessed. We randomized 724 patients (286 placebo, 438 dupilumab); mean CRSwNP duration was 11 years; 63% had prior sinonasal surgery. Mean baseline LoS was 2.74. Dupilumab produced rapid improvement in LoS, evident by day 3, which improved progressively throughout the study periods (least squares mean difference vs placebo -0.07 [95% CI -0.12 to -0.02]; nominal P < .05 at day 3, and -1.04 [-1.17 to -0.91]; P < .0001 at week 24). Dupilumab improved mean UPSIT by 10.54 (least squares mean difference vs placebo 10.57 [9.40-11.74]; P < .0001) at week 24 from baseline (score 13.90). Improvements were unaffected by CRSwNP duration, prior sinonasal surgery, or comorbid asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. Baseline olfaction scores correlated with all measured local and systemic type 2 inflammatory markers except serum total immunoglobulin E. Dupilumab produced rapid and sustained improvement in sense of smell, alleviating a cardinal symptom of severe CRSwNP.

Sections du résumé

BACKGROUND
Loss of smell (LoS) is one of the most troublesome and difficult-to-treat symptoms of severe chronic rhinosinusitis with nasal polyps (CRSwNP).
OBJECTIVE
To assess the impact of dupilumab on sense of smell in severe CRSwNP.
METHODS
In the randomized SINUS-24 and SINUS-52 studies, adults with severe CRSwNP received dupilumab 300 mg subcutaneously or matching placebo every 2 weeks for 24 or 52 weeks, respectively. Smell was assessed using daily patient-reported LoS score (0-3) and University of Pennsylvania Smell Identification Test (UPSIT; 0-40). Data from the 2 studies were pooled through week 24. Relationships between patient phenotypes and smell outcomes were also assessed.
RESULTS
We randomized 724 patients (286 placebo, 438 dupilumab); mean CRSwNP duration was 11 years; 63% had prior sinonasal surgery. Mean baseline LoS was 2.74. Dupilumab produced rapid improvement in LoS, evident by day 3, which improved progressively throughout the study periods (least squares mean difference vs placebo -0.07 [95% CI -0.12 to -0.02]; nominal P < .05 at day 3, and -1.04 [-1.17 to -0.91]; P < .0001 at week 24). Dupilumab improved mean UPSIT by 10.54 (least squares mean difference vs placebo 10.57 [9.40-11.74]; P < .0001) at week 24 from baseline (score 13.90). Improvements were unaffected by CRSwNP duration, prior sinonasal surgery, or comorbid asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. Baseline olfaction scores correlated with all measured local and systemic type 2 inflammatory markers except serum total immunoglobulin E.
CONCLUSIONS
Dupilumab produced rapid and sustained improvement in sense of smell, alleviating a cardinal symptom of severe CRSwNP.

Identifiants

pubmed: 34628065
pii: S2213-2198(21)01104-1
doi: 10.1016/j.jaip.2021.09.037
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
dupilumab 420K487FSG

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

1086-1095.e5

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Joaquim Mullol (J)

Hospital Clínic-IDIBAPS, Universitat de Barcelona, CIBERES, Barcelona, Catalonia, Spain. Electronic address: JMULLOL@clinic.cat.

Claus Bachert (C)

Ghent University, Ghent, Belgium; Karolinska Institutet, Stockholm, Sweden.

Nikhil Amin (N)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY.

Martin Desrosiers (M)

Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), Montreal, Quebec, Canada.

Peter W Hellings (PW)

University Hospitals Leuven, Leuven, Belgium.

Joseph K Han (JK)

Eastern Virginia Medical School, Norfolk, Va.

Roger Jankowski (R)

Université de Lorraine, ORL CHRU de Nancy, Nancy, France.

Jan Vodicka (J)

Faculty of Health Studies, University of Pardubice, Pardubice, Czech Republic.

Philippe Gevaert (P)

Ghent University, Ghent, Belgium.

Nadia Daizadeh (N)

Sanofi, Cambridge, Mass.

Asif H Khan (AH)

Sanofi, Chilly-Mazarin, France.

Siddhesh Kamat (S)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY.

Naimish Patel (N)

Sanofi, Bridgewater, NJ.

Neil M H Graham (NMH)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY.

Marcella Ruddy (M)

Regeneron Pharmaceuticals, Inc., Tarrytown, NY.

Heribert Staudinger (H)

Sanofi, Bridgewater, NJ.

Leda P Mannent (LP)

Sanofi, Chilly-Mazarin, France.

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Classifications MeSH