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Dupilumab in chronic rhinosinusitis without nasal polyps: randomized phase 2 trial (ORION)
S E Lee1, A T Peters2, P Gevaert3
1Department of Otolaryngology-Head and Neck Surgery, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, United States.
Rhinology
|July 17, 2026
Summary
Dupilumab improved sinus imaging scores in adults with severe chronic rhinosinusitis with nasal polyps (CRSsNP) and high eosinophil counts. The treatment showed a trend toward symptom improvement, indicating potential benefits for this patient group.
Area of Science:
- Immunology
- Otolaryngology
- Radiology
Background:
- Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the upper airways.
- Type 2 inflammation is a key driver of CRS, leading to symptoms like nasal obstruction and reduced smell.
- Nasal polyps can be present (CRSwNP) or absent (CRSsNP) in CRS.
Purpose of the Study:
- To evaluate the efficacy of dupilumab in improving radiographic features of chronic rhinosinusitis without nasal polyps (CRSsNP).
- To assess the impact of dupilumab on symptom scores and olfactory function in patients with severe, uncontrolled CRSsNP.
Main Methods:
- A phase 2, randomized, double-blind, placebo-controlled study (ORION) was conducted.
- Adults with uncontrolled CRSsNP and screening blood eosinophil count (sBEC) ≥300 cells/μL received dupilumab or placebo for 24-52 weeks.
- Key endpoints included changes in Lund-Mackay CT score (LMK-CT), Total Symptom Score (sTSS), University of Pennsylvania Smell Identification Test (UPSIT), and SNOT-22 score.
Main Results:
- Dupilumab treatment led to a significant reduction in LMK-CT scores compared to placebo.
- A trend towards improvement was observed in sinonasal symptoms (sTSS, SNOT-22) and smell identification (UPSIT) at week 24.
- Adverse events were comparable between the dupilumab and placebo groups.
Conclusions:
- Dupilumab demonstrated efficacy in improving sinus imaging outcomes in severe, uncontrolled CRSsNP with elevated eosinophil counts.
- The study suggests dupilumab may offer therapeutic benefits for sinonasal symptoms in this specific patient population.
- Further research may explore long-term efficacy and broader applications of dupilumab in CRS.