TY - JOUR
T1 - Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma
AU - Laidlaw, Tanya M.
AU - Bachert, Claus
AU - Amin, Nikhil
AU - Desrosiers, Martin
AU - Hellings, Peter W.
AU - Mullol, Joaquim
AU - Maspero, Jorge F.
AU - Gevaert, Philippe
AU - Zhang, Mei
AU - Mao, Xuezhou
AU - Khan, Asif H.
AU - Kamat, Siddhesh
AU - Patel, Naimish
AU - Graham, Neil M.H.
AU - Ruddy, Marcella
AU - Staudinger, Heribert
AU - Mannent, Leda P.
N1 - Funding Information:
The authors thank Nora Crikelair and Dianne Barry for providing publications support, Nadia Daizadeh for providing support with the statistical analysis, and Sinéad Holland, PhD, of Excerpta Medica for providing medical writing and editorial assistance, funded by Sanofi Genzyme and Regeneron Pharmaceuticals Inc.
Funding Information:
Disclosures: Dr Laidlaw has been a national and international scientific advisory board member of Allakos Inc, AstraZeneca, GlaxoSmithKline, and Sanofi-Aventis. Dr Bachert has been an advisory board member of ALK, ASIT Biotech, AstraZeneca, Intrexon Actobiotics, Novartis, Sanofi, and Stallergenes Greer. Dr Amin, Dr Graham, Dr Ruddy, and Mr Kamat are employees and shareholders of Regeneron Pharmaceuticals Inc. Dr Desrosiers has received clinical trial funding from AstraZeneca, GlaxoSmithKline, Probionase Therapies Inc, and Sanofi; has been an advisory board member of Regeneron Pharmaceuticals Inc and Sanofi; and has been an equity holder of Probionase Therapies Inc. Dr Hellings has been an advisory board member of Regeneron Pharmaceuticals Inc and Sanofi. Dr Mullol has received clinical trial funding or speaker fees and has been an advisory board member of AstraZeneca, Genentech Inc, GlaxoSmithKline, Menarini, Mitsubishi Tanabe Pharma Corporation, MSD, Mylan/MEDA Pharma, Novartis, Regeneron Pharmaceuticals Inc, Sanofi Genzyme, UCB, and Uriach Group; and received research grants from Mylan/MEDA Pharma and Uriach Group. Dr Maspero has been a consultant for AstraZeneca, Sanofi, and Teva Pharmaceutical Industries Ltd; received speaker fees from GlaxoSmithKline, Menarini, Novartis, and Uriach; and received research grants from Novartis. Dr Gevaert has received clinical trial funding and been an advisory board member of 3NT Medical, ALK, Argenx, Genentech Inc, Novartis, Regeneron Pharmaceuticals Inc, Roche, Sanofi, and Stallergenes Greer. Dr Zhang, Dr Mao, Dr Khan, Dr Patel, Dr Staudinger, and Dr Mannent are employees and may hold stock or stock options in Sanofi. Funding: This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals Inc.
Publisher Copyright:
© 2021
PY - 2021/5
Y1 - 2021/5
N2 - Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and type 2 asthma share the same inflammatory pathophysiology and are frequent comorbidities. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin 4 and interleukin 13, which are key and central drivers of type 2 inflammation. Objective: We report the effect of dupilumab vs placebo on outcome measures of the upper and lower airways and health-related quality of life (HRQoL) in the pooled population of patients with CRSwNP and comorbid asthma from the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies. Methods: In these randomized, double-blind, placebo-controlled trials, patients received subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks on a background of mometasone furoate nasal spray. Changes from baseline at week 24 in the upper and lower airway outcome measures are reported. Results: Of the 724 patients randomized, 428 (59.1%) had comorbid asthma. In patients with asthma at week 24, dupilumab vs placebo improved the nasal polyp score (−2.04), patient-reported nasal congestion score (−1.04), Lund-Mackay computed tomography scan score (−6.43), peak nasal inspiratory flow (46.15 L/min), and 22-item sinonasal outcome test score (−21.42; all P < .001). The forced expiratory volume in 1 second and 6-item asthma control questionnaire scores were also markedly improved with dupilumab vs placebo. The most common adverse events (nasopharyngitis, headache, injection-site erythema, worsening of nasal polyposis, and asthma) were more frequent with placebo than dupilumab. Conclusion: Dupilumab improved upper and lower airway outcome measures and HRQoL in patients with severe CRSwNP and comorbid asthma and was well tolerated. Trial Registration: ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52).
AB - Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and type 2 asthma share the same inflammatory pathophysiology and are frequent comorbidities. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin 4 and interleukin 13, which are key and central drivers of type 2 inflammation. Objective: We report the effect of dupilumab vs placebo on outcome measures of the upper and lower airways and health-related quality of life (HRQoL) in the pooled population of patients with CRSwNP and comorbid asthma from the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies. Methods: In these randomized, double-blind, placebo-controlled trials, patients received subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks on a background of mometasone furoate nasal spray. Changes from baseline at week 24 in the upper and lower airway outcome measures are reported. Results: Of the 724 patients randomized, 428 (59.1%) had comorbid asthma. In patients with asthma at week 24, dupilumab vs placebo improved the nasal polyp score (−2.04), patient-reported nasal congestion score (−1.04), Lund-Mackay computed tomography scan score (−6.43), peak nasal inspiratory flow (46.15 L/min), and 22-item sinonasal outcome test score (−21.42; all P < .001). The forced expiratory volume in 1 second and 6-item asthma control questionnaire scores were also markedly improved with dupilumab vs placebo. The most common adverse events (nasopharyngitis, headache, injection-site erythema, worsening of nasal polyposis, and asthma) were more frequent with placebo than dupilumab. Conclusion: Dupilumab improved upper and lower airway outcome measures and HRQoL in patients with severe CRSwNP and comorbid asthma and was well tolerated. Trial Registration: ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52).
UR - http://www.scopus.com/inward/record.url?scp=85101085181&partnerID=8YFLogxK
U2 - 10.1016/j.anai.2021.01.012
DO - 10.1016/j.anai.2021.01.012
M3 - Article
C2 - 33465455
AN - SCOPUS:85101085181
VL - 126
SP - 584-592.e1
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
SN - 1081-1206
IS - 5
ER -