Claus Bachert1, S James Zinreich2, Peter W Hellings3, Joaquim Mullol4, Daniel L Hamilos5, Philippe Gevaert1, Robert M Naclerio6, Nikhil Amin7, Vijay N Joish8, Chunpeng Fan9, Donghui Zhang9, Heribert Staudinger9, Gianluca Pirozzi9, Neil M H Graham7, Asif Khan10, Leda P Mannent10. 1. Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium, and Clintec, Karolinska Institute, Stockholm, Sweden. 2. Division of Neuroradiology, Department of Radiology, Johns Hopkins Hospital, Baltimore, MD, USA. 3. Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium. 4. Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, and Rhinology Unit and Smell Clinic, Department of Otorhinolaryngo logy, Hospital Clinic, Universitat de Barcelona, CIBERES, Barcelona, Catalonia, Spain. 5. Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA. 6. Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA. 7. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 8. Formerly employed at Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 9. Sanofi, Bridgewater, NJ, USA. 10. Sanofi, Chilly-Mazarin, France.
Abstract
BACKGROUND:Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with substantial sinus opacification. In a phase 2a study (NCT01920893), dupilumab, a fully human anti-IL-4Rα monoclonal antibody, improved outcomes in CRSwNP refractory to intranasal corticosteroids. We evaluated dupilumab’s effect on sinus opacification in relation to effects on nasal polyp burden, symptoms, and health-related quality of life (HRQoL) in patients with CRSwNP. METHODOLOGY: 16-week randomized, double-blind, placebo-controlled, parallel-group study in 60 adults with CRSwNP. Patients received weekly subcutaneous dupilumab 300-mg or placebo and daily mometasone furoate nasal spray. Sinus opacification was assessed using standard and Zinreich-modified Lundâ€"Mackay (zLMK) scoring. Correlation was assessed between zLMK score and CRSwNP endpoints, including nasal polyp score (NPS), SNOT-22, daily symptom scores, and UPSIT smell-test score. RESULTS: Baseline characteristics were similar across treatment groups. Mean plus/minus SD baseline LMK scores of 18.7 plus/minus 5.5 (placebo) and 18.6 plus/minus 5.0 (dupilumab) indicated severe disease with extensive opacification involving all sinuses. Baseline LMK and LMK scores correlated with NPS severity and loss of sense of smell (daily symptoms; SNOT-22 smell/taste; loss of sense of smell [UPSIT]). At Week 16, dupilumab-treated patients had significantly improved sinus opacification measured by LMK in all individual sinuses vs placebo. Dupilumab also showed similar efficacy with zLMK, with only small differences from LMK, and correlated with SNOT22 smell/taste. The most common adverse events were nasopharyngitis, injection-site reactions, and headache. CONCLUSIONS: In patients with CRSwNP, baseline LMK showed extensive sinus opacification and correlated with symptoms, HRQoL, and hyposmia. Dupilumab treatment reduces opacification across all sinuses and related symptoms in patients with CRSwNP.
RCT Entities:
BACKGROUND:Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with substantial sinus opacification. In a phase 2a study (NCT01920893), dupilumab, a fully human anti-IL-4Rα monoclonal antibody, improved outcomes in CRSwNP refractory to intranasal corticosteroids. We evaluated dupilumab’s effect on sinus opacification in relation to effects on nasal polyp burden, symptoms, and health-related quality of life (HRQoL) in patients with CRSwNP. METHODOLOGY: 16-week randomized, double-blind, placebo-controlled, parallel-group study in 60 adults with CRSwNP. Patients received weekly subcutaneous dupilumab 300-mg or placebo and daily mometasone furoate nasal spray. Sinus opacification was assessed using standard and Zinreich-modified Lundâ€"Mackay (zLMK) scoring. Correlation was assessed between zLMK score and CRSwNP endpoints, including nasal polyp score (NPS), SNOT-22, daily symptom scores, and UPSIT smell-test score. RESULTS: Baseline characteristics were similar across treatment groups. Mean plus/minus SD baseline LMK scores of 18.7 plus/minus 5.5 (placebo) and 18.6 plus/minus 5.0 (dupilumab) indicated severe disease with extensive opacification involving all sinuses. Baseline LMK and LMK scores correlated with NPS severity and loss of sense of smell (daily symptoms; SNOT-22 smell/taste; loss of sense of smell [UPSIT]). At Week 16, dupilumab-treated patients had significantly improved sinus opacification measured by LMK in all individual sinuses vs placebo. Dupilumab also showed similar efficacy with zLMK, with only small differences from LMK, and correlated with SNOT22 smell/taste. The most common adverse events were nasopharyngitis, injection-site reactions, and headache. CONCLUSIONS: In patients with CRSwNP, baseline LMK showed extensive sinus opacification and correlated with symptoms, HRQoL, and hyposmia. Dupilumab treatment reduces opacification across all sinuses and related symptoms in patients with CRSwNP.
Authors: Andrew Thamboo; S Kilty; I Witterick; Y Chan; C J Chin; A Janjua; A Javer; J Lee; E Monterio; B Rotenberg; J Scott; K Smith; D D Sommer; L Sowerby; M Tewfik; E Wright; M Desrosiers Journal: J Otolaryngol Head Neck Surg Date: 2021-03-09