Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP

Claus Bachert, S. James Zinreich, Peter W. Hellings, Joaquim Mullol, Daniel L. Hamilos, Philippe Gevaert, Robert M. Naclerio, Nikhil Amin, Vijay N. Joish, Chunpeng Fan, Donghui Zhang, Heribert Staudinger, Gianluca Pirozzi, Neil M.H. Graham, Asif Khan, Leda P. Mannent

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalRhinology
Volume58
Issue number1
DOIs
StatePublished - Feb 1 2020

ASJC Scopus subject areas

  • Otorhinolaryngology

Fingerprint Dive into the research topics of 'Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP'. Together they form a unique fingerprint.

  • Cite this

    Bachert, C., Zinreich, S. J., Hellings, P. W., Mullol, J., Hamilos, D. L., Gevaert, P., Naclerio, R. M., Amin, N., Joish, V. N., Fan, C., Zhang, D., Staudinger, H., Pirozzi, G., Graham, N. M. H., Khan, A., & Mannent, L. P. (2020). Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP. Rhinology, 58(1), 10-17. https://doi.org/10.4193/Rhin18.282