Long-term efficacy of dupilumab in asthma with or without chronic rhinosinusitis and nasal polyps.


Journal

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
ISSN: 1534-4436
Titre abrégé: Ann Allergy Asthma Immunol
Pays: United States
ID NLM: 9503580

Informations de publication

Date de publication:
02 2023
Historique:
received: 23 08 2022
revised: 21 10 2022
accepted: 02 11 2022
pubmed: 11 11 2022
medline: 8 2 2023
entrez: 10 11 2022
Statut: ppublish

Résumé

Coexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP. To evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP. In TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose. Patients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS. Long-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma. ClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028.

Sections du résumé

BACKGROUND
Coexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP.
OBJECTIVE
To evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP.
METHODS
In TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose.
RESULTS
Patients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS.
CONCLUSION
Long-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028.

Identifiants

pubmed: 36356712
pii: S1081-1206(22)01912-3
doi: 10.1016/j.anai.2022.11.006
pii:
doi:

Substances chimiques

Adrenal Cortex Hormones 0
Anti-Asthmatic Agents 0
Antibodies, Monoclonal, Humanized 0
dupilumab 420K487FSG

Banques de données

ClinicalTrials.gov
['NCT02134028', 'NCT02414854', 'NCT02528214']

Types de publication

Controlled Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

215-224

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Patrick Berger (P)

Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Pessac, France; INSERM, U1045, Pessac, France; Service d'exploration fonctionnelles respiratoires, CHU de Bordeaux, Pessac, France. Electronic address: patrick.berger@u-bordeaux.fr.

Andrew Menzies-Gow (A)

Royal Brompton and Harefield Hospitals, London, United Kingdom.

Anju T Peters (AT)

Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Piotr Kuna (P)

Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź, Łódź, Poland.

Klaus F Rabe (KF)

Airway Research Center North (ARCN), LungenClinic Grosshansdorf (member of the German Center for Lung Research [DZL]), Grosshansdorf, Germany; Airway Research Center North (ARCN), Christian-Albrechts University (member of the German Center for Lung Research [DZL]), Kiel, Germany.

Arman Altincatal (A)

Sanofi, Cambridge, Massachusetts.

Xavier Soler (X)

Regeneron Pharmaceuticals, Inc, Tarrytown, New York.

Nami Pandit-Abid (N)

Sanofi, Bridgewater, New Jersey.

Shahid Siddiqui (S)

Regeneron Pharmaceuticals, Inc, Tarrytown, New York.

Juby A Jacob-Nara (JA)

Sanofi, Bridgewater, New Jersey.

Yamo Deniz (Y)

Regeneron Pharmaceuticals, Inc, Tarrytown, New York.

Paul J Rowe (PJ)

Sanofi, Bridgewater, New Jersey.

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Classifications MeSH