Dupilumab for patients with allergic fungal rhinosinusitis.

BACKGROUND

Allergic fungal rhinosinusitis (AFRS) is a severe subtype of chronic rhinosinusitis characterized by fungal hypersensitivity and accentuated type 2 inflammation. Dupilumab-a fully human mAb blocking IL-4/13, approved for type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps-may benefit patients with AFRS.

OBJECTIVE

We sought to understand the effect of dupilumab in AFRS.

METHODS

In this phase 3 trial, patients with AFRS age ≥6 years were randomized to dupilumab or matched placebo for 52 weeks. The primary end point was Lund-Mackay computed tomography score, quantifying sinus opacification, at 52 weeks. Secondary end points were multiplicity-controlled and hierarchically tested.

RESULTS

At week 52, the dupilumab group's (n = 33) Lund-Mackay computed tomography scores improved versus those of the placebo group (n = 29) (least squares mean difference [LSMD]: -7.36 [95% CI: -9.38 to -5.35]; P < .001). At week 24, dupilumab improved nasal congestion score (LSMD: -0.87 [95% CI: -1.18 to -0.56]), total symptom score (LSMD: -2.18 [95% CI: -3.04 to -1.32]), and nasal polyp score (LSMD: -2.36 [95% CI: -3.31 to -1.41]) versus placebo, and further decreased nasal polyp score to -2.77 (95% CI: -3.82 to -1.72) (all P < .001) at week 52. Dupilumab lowered the risk of receiving systemic corticosteroids and/or undergoing sinonasal surgery versus 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%).

CONCLUSIONS

In patients with AFRS, dupilumab versus placebo demonstrated significant improvement in radiographic, endoscopic, clinical, and quality-of-life outcomes, and need for systemic corticosteroids and/or surgery. Dupilumab was well tolerated. (LIBERTY AFRS AIMS, NCT04684524).