Dupilumab in chronic rhinosinusitis without nasal polyps: randomized phase 2 trial (ORION)

Chronic rhinosinusitis (CRS) is often driven by type 2 inflammation and is characterized by nasal obstruction/ discharge, facial pain/pressure, and/or reduced smell, either with or without nasal polyps (CRSwNP or CRSsNP).

To test whether dupilumab improves radiographic features in CRSsNP.

ORION (NCT04678856), a phase 2, randomized, multicenter, double blind, placebo-controlled study, assessed dupilumab efficacy and safety in adults with uncontrolled CRSsNP. Patients were randomized 1:1 to dupilumab or placebo for 24 to 52 weeks. Endpoints included changes from baseline at week 24 in Lund-Mackay computed tomography (LMK-CT) score (dupilumab only [primary] and vs placebo [secondary]), sinus Total Symptom Score (sTSS), University of Pennsylvania Smell Identification Test (UPSIT) score, and 22-item Sino-Nasal Outcome Test(SNOT-22) score. Primary analysis was conducted in the intention-to-treat population with screening blood eosinophil count (sBEC) ≥300 cells/μL. Safety data were evaluated in all patients.

Seventy-one patients were randomized (dupilumab, n = 38; placebo, n = 33). In the dupilumab group with sBEC ≥300 cells/μL (n = 16), mean (95% CI) week 24 change from baseline in LMK-CT was -6.63 (-8.71 to -4.54); week 24 mean differences vs placebo (95% CI) for LMK-CT, sTSS, UPSIT, and SNOT-22 were -5.95 (-8.38 to -3.51), -1.43 ( 3.28 to 0.41), 5.91 (-1.56 to 13.38), and -14.71 (-34.35 to 4.94). Treatment-emergent adverse events were balanced between treatment groups.

Dupilumab was associated with improvement in LMK-CT score and a trend toward improvement in sinonasal symptoms at week 24 in adults with severe, uncontrolled CRSsNP with sBEC ≥300 cells/μL.