Journal of Asthma and Allergy (May 2022)

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

  • Bachert C,
  • Khan AH,
  • Hopkins C,
  • Blaiss MS,
  • Soler ZM,
  • Nash S,
  • Siddiqui S,
  • Praestgaard A,
  • Deniz Y,
  • Rowe PJ,
  • Jacob-Nara JA

Journal volume & issue
Vol. Volume 15
pp. 557 – 563

Abstract

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Claus Bachert,1– 3 Asif H Khan,4 Claire Hopkins,5 Michael S Blaiss,6 Zachary M Soler,7 Scott Nash,8 Shahid Siddiqui,8 Amy Praestgaard,9 Yamo Deniz,8 Paul J Rowe,10 Juby A Jacob-Nara10 1Upper Airways Research Laboratory and Department of Otorhinolaryngology, Ghent University, Ghent, Belgium; 2Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden; 3International Airway Research Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Global Medical Affairs, Sanofi, Chilly-Mazarin, France; 5Department of Otorhinolaryngology – Head and Neck Surgery, Guy’s and St Thomas’ Hospitals, London, UK; 6Department of Pediatrics, Medical College of Georgia at Augusta University, Augusta, GA, USA; 7Department of Otolaryngology – Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA; 8Medical Affairs, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 9Department of Biostatistics, Sanofi, Cambridge, MA, USA; 10Global Medical Affairs, Sanofi, Bridgewater, NJ, USACorrespondence: Claus Bachert, Upper Airways Research Laboratory and Department of Otorhinolaryngology, Ghent University, Ghent, B-9000, Belgium, Tel +32 9332 5513, Email [email protected]: 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.Graphical Abstract: Keywords: chronic rhinosinusitis with nasal polyps, dupilumab, nasal polyp score, nasal congestion

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