Dupilumab for patients with allergic fungal rhinosinusitis.

Abstract

Allergic fungal rhinosinusitis (AFRS) is a severe subtype of chronic rhinosinusitis characterized by fungal hypersensitivity and accentuated type 2 inflammation. Dupilumab-a fully human monoclonal antibody blocking interleukin-4/13, approved for type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps-may benefit patients with AFRS. In this phase 3 trial, patients with AFRS aged ≥6 years were randomized to dupilumab or matched placebo for 52 weeks. The primary end point was Lund-Mackay computed tomography (LMK-CT) score, quantifying sinus opacification, at 52 weeks. Secondary end points were multiplicity-controlled and hierarchically tested. At week 52, dupilumab (N=33) improved LMK-CT scores vs placebo (N=29) (LSMD -7.36 [95% CI, -9.38 to -5.35]; P<.001). At week 24, dupilumab improved nasal congestion score (-0.87 [-1.18 to -0.56]), total symptom score (-2.18 [-3.04 to -1.32]), and nasal polyp score (NPS; -2.36 [-3.31 to -1.41]) vs placebo, and further decreased NPS to -2.77 (-3.82 to -1.72) (all P<.001) at week 52. Dupilumab lowered the risk of receiving systemic corticosteroids and/or undergoing sinonasal surgery vs placebo by 92% (risk difference -29.1% [95% CI, -46.42 to -11.79]; P=.0010). In patients with comorbid asthma, dupilumab also benefited asthma measures. The proportion of patients having treatment-emergent adverse events was similar between dupilumab and placebo (69.7% and 78.6%). In patients with AFRS, dupilumab vs placebo demonstrated significant improvement in radiographic, endoscopic, clinical, quality-of-life outcomes, and need for systemic corticosteroids and/or surgery. Dupilumab was well tolerated. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY AFRS AIMS ClinicalTrials.gov number, NCT04684524.).