Rapid and Continuing Improvements in Nasal Symptoms with Dupilumab in Patients with Severe CRSwNP

Claus Bachert; Asif H Khan; Claire Hopkins; Michael S Blaiss; Zachary M Soler; Scott Nash; Shahid Siddiqui; Amy Praestgaard; Yamo Deniz; Paul J Rowe; Juby A Jacob-Nara

doi:10.2147/JAA.S355391

Rapid and Continuing Improvements in Nasal Symptoms with Dupilumab in Patients with Severe CRSwNP

J Asthma Allergy. 2022 May 4:15:557-563. doi: 10.2147/JAA.S355391. eCollection 2022.

Authors

Claus Bachert^{1

2

3}, Asif H Khan⁴, Claire Hopkins⁵, Michael S Blaiss⁶, Zachary M Soler⁷, Scott Nash⁸, Shahid Siddiqui⁸, Amy Praestgaard⁹, Yamo Deniz⁸, Paul J Rowe¹⁰, Juby A Jacob-Nara¹⁰

Affiliations

¹ Upper Airways Research Laboratory and Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
² Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
³ International Airway Research Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
⁴ Global Medical Affairs, Sanofi, Chilly-Mazarin, France.
⁵ Department of Otorhinolaryngology - Head and Neck Surgery, Guy's and St Thomas' Hospitals, London, UK.
⁶ Department of Pediatrics, Medical College of Georgia at Augusta University, Augusta, GA, USA.
⁷ Department of Otolaryngology - Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA.
⁸ Medical Affairs, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
⁹ Department of Biostatistics, Sanofi, Cambridge, MA, USA.
¹⁰ Global Medical Affairs, Sanofi, Bridgewater, NJ, USA.

Abstract

Purpose: In the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly improved the co-primary endpoints of change from baseline to Week 24 in nasal polyp score (NPS) and nasal congestion/obstruction (NC) vs placebo on background intranasal corticosteroids (standard of care [SOC]). This post hoc analysis of SINUS-24/-52 investigated the direction and magnitude of within-patient change in these endpoints over time.

Methods: NPS (scale 0-8) was assessed at Weeks 4, 8, 16, 24, 40, and 52 in SINUS-52 and Weeks 8, 16, and 24 in SINUS-24. Daily patient-reported NC scores (0 [no symptoms]-3 [severe symptoms]) were averaged over 28 days. Within-patient changes from baseline were assessed through Week 24 in pooled SINUS-24/-52 (n = 438/286 dupilumab/SOC) and through Week 52 in SINUS-52 (n = 150/153).

Results: In SINUS-52, NPS improved in 70.0% of dupilumab-treated patients at Week 4 vs 31.8% with SOC (odds ratio [OR] 5.2 [95% confidence interval 3.1-8.8]) and 78.7% vs 28.2% at Week 52 (OR 10.6 [6.0-18.7]) (all p < 0.0001). NC improved in 73.3% of dupilumab-treated patients at Week 4 vs 46.7% with SOC (OR 3.2 [2.0-5.3]) and 86.9% vs 50.7% at Week 52 (OR 6.4 [3.5-11.5]) (all p < 0.0001). Clinically meaningful (≥1 point) improvements in NPS occurred in 55.7% and 72.3% of dupilumab-treated patients at Weeks 4 and 52, respectively, vs 16.9% and 16.2% with SOC. Clinically meaningful (≥1 point) improvements in NC occurred in 16.7% and 67.6% of dupilumab-treated patients at Weeks 4 and 52, respectively, vs 3.9% and 20.8% with SOC. At Week 52, NPS worsening from baseline was observed in 5.7% of dupilumab-treated patients vs 40.1% with SOC and NC worsening in 2.1% vs 20.8%, respectively.

Conclusion: Dupilumab provided rapid, continuing, and clinically relevant improvements over time in NPS and NC in most patients with severe CRSwNP in the SINUS studies.

Keywords: chronic rhinosinusitis with nasal polyps; dupilumab; nasal congestion; nasal polyp score.

Grants and funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.