@article{80f074a3b1b942b3971ec2651d4b93e8,
title = "Olfactory Outcomes With Dupilumab in Chronic Rhinosinusitis With Nasal Polyps",
abstract = "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.",
keywords = "Anosmia, Chronic rhinosinusitis with nasal polyps, Dupilumab, Sense of smell, Type 2 inflammation",
author = "Joaquim Mullol and Claus Bachert and Nikhil Amin and Martin Desrosiers and Hellings, {Peter W.} and Han, {Joseph K.} and Roger Jankowski and Jan Vodicka and Philippe Gevaert and Nadia Daizadeh and Khan, {Asif H.} and Siddhesh Kamat and Naimish Patel and Graham, {Neil M.H.} and Marcella Ruddy and Heribert Staudinger and Mannent, {Leda P.}",
note = "Funding Information: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Sanofi and Regeneron Pharmaceuticals, Inc., in collaboration with the academic clinical investigators, provided input on the design and conduct of the study; oversaw the collection, management, and statistical analysis of data; and contributed to the interpretation of the data and the preparation, review, and submission of the manuscript. The final decision on manuscript submission was made by the authors; the sponsors did not have the right to veto or require submission or publication.Conflicts of interest: J. Mullol has participated in advisory boards for, received research grants from, or participated in speakers' bureaus for ALK-Abell{\'o}, AstraZeneca, Genentech, GlaxoSmithKline, Glenmark, Menarini, Mitsubishi Tanabe Pharma, MSD, Mylan-Meda Pharmaceuticals (Viatris), Novartis, Proctor & Gamble, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB Pharma, and Uriach Group. C. Bachert has participated in advisory boards for and/or received speakers' fees from ALK, AstraZeneca, GlaxoSmithKline, Mylan, Novartis, Sanofi, and Stallergenes Greer. N. Amin and S. Kamat are employees of and may hold stock or stock options in Regeneron Pharmaceuticals, Inc. N. M. H. Graham and M. Ruddy are former employees of and may hold stock or stock options in Regeneron Pharmaceuticals, Inc. M. Desrosiers has received clinical trial funding from AstraZeneca, GlaxoSmithKline, Probionase Therapies, and Sanofi; has been an advisory board member of Regeneron Pharmaceuticals, Inc. and Sanofi; and is an equity holder of Probionase Therapies. P. W. Hellings has been an advisory board member of Regeneron Pharmaceuticals, Inc. and Sanofi. J. K. Han has participated in advisory boards for Sanofi. R. Jankowski has participated in advisory boards for ALK, Laboratoire de la Mer, Regeneron Pharmaceuticals, Inc., and Sanofi. J. Vodicka has received clinical trial funding from Novartis. P. Gevaert has received clinical trial funding from and been an advisory board member for 3NT, ALK, Argenx, Genentech, Novartis, Regeneron Pharmaceuticals, Inc., Roche, Sanofi, and Stallergenes Greer. A. H. Khan, N. Patel, H. Staudinger, and L. P. Mannent are employees of and may hold stock or stock options in Sanofi. N. Daizadeh is a former employee of and may hold stock or stock options in Sanofi.We thank Mei Zhang, PhD, Xuezhou Mao, PhD, and J{\'e}r{\^o}me Msihid, MSc, of Sanofi for statistical analyses, and Matt Lewis, PhD, of Adelphi Communications Ltd (Macclesfield, UK) for medical writing support, which was funded by Sanofi (Bridgewater, NJ) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY) in accordance with Good Publication Practice (GPP3) guidelines. J. Mullol had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. J. Mullol, C. Bachert, N. Amin, M. Desrosiers, A. H. Khan, S. Kamat, N. M. H. Graham, H. Staudinger, and L. P. Mannent were responsible for the study concept and design. J. Mullol, C. Bachert, N. Amin, M. Desrosiers, P. W. Hellings, J. K. Han, R. Jankowski, J. Vodicka, P. Gevaert, N. Daizadeh, A. H. Khan, S. Kamat, N. Patel, N. M. H. Graham, M. Ruddy, H. Staudinger, and L. P. Mannent were responsible for acquisition, analysis, or interpretation of data. J. Mullol, C. Bachert, N. Amin, M. Desrosiers, P. W. Hellings, J. K. Han, R. Jankowski, J. Vodicka, P. Gevaert, N. Daizadeh, A. H. Khan, S. Kamat, N. Patel, N. M. H. Graham, M. Ruddy, H. Staudinger, and L. P. Mannent were responsible for drafting or critical revision of the manuscript for important intellectual content. Qualified researchers may request access to patient-level data and related study documents including clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data-sharing criteria, eligible studies, and process for requesting access can be found at https://www.clinicalstudydatarequest.com. Funding Information: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc . Sanofi and Regeneron Pharmaceuticals, Inc., in collaboration with the academic clinical investigators, provided input on the design and conduct of the study; oversaw the collection, management, and statistical analysis of data; and contributed to the interpretation of the data and the preparation, review, and submission of the manuscript. The final decision on manuscript submission was made by the authors; the sponsors did not have the right to veto or require submission or publication. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = apr,
doi = "10.1016/j.jaip.2021.09.037",
language = "English",
volume = "10",
pages = "1086--1095.e5",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
number = "4",
}