Q. What challenges are associated with the treatment of AFRS in paediatric and adult patients?

Standard-of-care treatments are surgery and long-term topical corticosteroids with courses of systemic corticosteroids commonly prescribed for recurrent symptoms and polyps. Systemic corticosteroids can pose safety risks when used long-term. Additionally, prior to dupilumab, no treatments were specifically indicated for AFRS.

Q. What is the mechanism of action of dupilumab and what was the rationale for investigating the IL-4/IL-13 inhibitor in AFRS?

Dupilumab targets a shared receptor (IL-4Rα) for the IL-4 and IL-13 immune signalling molecules, or cytokines. Both of these are key drivers of type 2 inflammation, which is known to play an important role in chronic rhinosinusitis with nasal polyps, a closely related disease to AFRS. Given this, there was a strong scientific rationale for investigating dupilumab in AFRS.

Q. What were the aims, design and clinical endpoints of the LIBERTY-AIMS study?

The aim of the study was to evaluate the efficacy and safety of dupilumab in adults and children aged 6 years and older with AFRS. Patients were randomized 1:1 to receive either dupilumab or placebo, and dupilumab was administered based on age and weight. The primary endpoint assessed change from baseline in sinus opacification, a way to measure the extent of tissue inflammation and mucus blocking the sinuses where there should be air flow. Secondary endpoints included change from baseline in patient-reported nasal congestion and change from baseline in nasal polyp score, a measure of nasal polyp size.

Q. What were the key efficacy and safety findings from the Phase 3 study?

Dupilumab significantly reduced sinus opacification, nasal polyp size, and nasal congestion/severity compared to placebo. Additionally, all patients on dupilumab achieved better thresholds of reduction for sinus opacification and nasal congestion at Week 52, and more patients on dupilumab had at least 1-point improvement on the scale measuring nasal polyp size at Weeks 12, 24, 36 and 52, compared to placebo. The proportion of patients experiencing treatment emergent adverse events was similar across the two groups, but slightly lower for patients receiving dupilumab.

Q. Following the recent FDA approval, what impact will dupilumab have as the first and only therapy for AFRS?

Dupilumab provides AFRS patients an alternative treatment to revision sinus surgery or recurrent courses of oral steroids for recurrent nasal polyps. In addition, it inhibits two key drivers of type 2 inflammation, the biological process driving both the sinus inflammation and the intense allergic hypersensitivity to fungi that incite allergic rhinitis symptoms.