Dupilumab Improves Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps and Coexisting Asthma Irrespective of Baseline Asthma Characteristics

Abstract

Purpose

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease frequently coexisting with other type 2 conditions including asthma and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Coexisting asthma leads to increased CRSwNP symptom burden. Dupilumab, a monoclonal antibody that blocks the shared receptor component for interleukin-4 and -13, demonstrated efficacy in adults with severe CRSwNP in the Phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies, including in patients with coexisting asthma/NSAID-ERD. However, the impact of different asthma characteristics on dupilumab treatment in this population is unknown. We report CRSwNP and asthma outcomes with dupilumab in patients with CRSwNP and coexisting asthma according to baseline asthma characteristics.

Methods

Change from baseline at Week 24 (pooled studies) and Week 52 (SINUS-52) in CRSwNP outcomes (nasal polyp score, nasal congestion, 22-item Sino-Nasal Outcome Test [SNOT-22], loss of smell score, University of Pennsylvania Smell Identification Test) and asthma outcomes (5-item Asthma Control Questionnaire [ACQ-5], pre-bronchodilator forced expiratory volume in 1 second [FEV₁]) were analyzed post hoc for placebo and dupilumab 300 mg every 2 weeks according to baseline blood eosinophils ≥150/≥300 cells/µL, ACQ-5 scores <1.5/≥1.5, and FEV₁ <80%.

Results

In the pooled studies, 428/724 patients (59.1%) had coexisting asthma, of which 181/428 (42.3%) had coexisting NSAID-ERD. Dupilumab significantly improved all CRSwNP and asthma outcomes vs placebo at Week 24 (P < 0.001) regardless of baseline eosinophil or ACQ-5 category, or FEV₁ <80%. Similar magnitude of improvement was seen at Week 52 (SINUS-52) and in patients with NSAID-ERD (pooled studies, Week 24). By Week 24, improvements with dupilumab exceeded the minimum clinically important differences for ACQ-5 and SNOT-22 in 35.2% to 74.2% and 72.0% to 78.7% of patients, respectively.

Conclusion

Dupilumab improved CRSwNP outcomes in patients with CRSwNP and coexisting asthma, and improved asthma outcomes, regardless of differences in baseline asthma characteristics.

Keywords:

• chronic rhinosinusitis with nasal polyps
• dupilumab
• asthma

Abbreviations

ACQ-5, 5-item Asthma Control Questionnaire; ANCOVA, analysis of covariance; CI, confidence interval; CRSwNP, chronic rhinosinusitis with nasal polyps; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; HRQoL, health-related quality of life; ITT, intention-to-treat; LoS, loss of smell; LS, least squares; MCID, minimum clinically important difference; NC, nasal congestion; NPS, nasal polyp score; NSAID-ERD, non-steroidal anti-inflammatory drug-exacerbated respiratory disease; SNOT-22, 22-item Sino-Nasal Outcome Test; UPSIT, University of Pennsylvania Smell Identification Test.

Data Sharing Statement

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.vivli.org/.

Ethics Approval and Informed Consent

The studies were conducted in accordance with the Declaration of Helsinki, approved by the local institutional review board or ethics committee at each study site (Table S3), and all patients provided written informed consent.

Acknowledgments

This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov identifiers: NCT02912468 and NCT02898454. Medical writing support was provided by Olympia Gianfrancesco, PhD, of Adelphi Group, Macclesfield, UK, funded by Sanofi and Regeneron Pharmaceuticals Inc. in accordance with Good Publications Practice.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all of these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

WWB reports speaker fees from GlaxoSmithKline and Regeneron Pharmaceuticals Inc., consultancy fees from Arrowhead, AstraZeneca, Genentech, GlaxoSmithKline, Knopp Biosciences, Novartis, Regeneron Pharmaceuticals Inc., and Sanofi, grants or contracts from National Institutes of Health – National Heart, Lung, and Blood Institute and National Institutes of Health – National Institute of Allergy and Infectious Diseases, book royalties from Elsevier, and support for attending meetings and/or travel from GlaxoSmithKline, Regeneron Pharmaceuticals Inc., and Sanofi. IDP reports speaker fees from Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Regeneron Pharmaceuticals Inc., Sanofi, and Teva, payments for organizing educational events from AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals Inc., Sanofi, and Teva, consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Genentech, GlaxoSmithKline, Knopp Biosciences, Merck, Novartis, Regeneron Pharmaceuticals Inc., Sanofi, and Teva, international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Teva, research grants from Chiesi, payments to support FDA approval meetings from GlaxoSmithKline, and payments for use of the Leicester Cough Questionnaire (of which he is a co-patent holder of the rights) in clinical trials from Bayer, Insmed, and Merck, and served as an expert witness for a patent dispute involving AstraZeneca and Teva. He also reports a grant from Chiesi to support a Phase 2 clinical trial in Oxford. SS is a former employee of Regeneron Pharmaceuticals Inc. and may hold stock and/or stock options. AHK, AP, JAJ-N, and PJR are employees of Sanofi and may hold stock and/or stock options. SN and YD are employees of Regeneron Pharmaceuticals Inc. and may hold stock and/or stock options. The authors report no other conflicts of interest in this work.

Additional information

Funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov identifiers: NCT02912468 and NCT02898454.