Dupilumab efficacy in asthma patients with comorbid chronic rhinosinusitis or nasal polyposis (CRS/NP) in LIBERTY ASTHMA QUEST

Background: Dupilumab (DPL), a fully human anti-IL-4Rα mAb that inhibits IL-4/IL-13, is approved for treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. In a phase 3 study (NCT02414854), asthma patients (pts) aged ≥12 years, with no minimum baseline (BL) eosinophil requirement, uncontrolled with medium-to-high-dose ICS, plus 1 or 2 controllers received DPL 200/300mg or placebo (PBO) every 2 weeks for 52 weeks. DPL reduced severe exacerbations, improved FEV₁ and quality of life measures, and was generally well tolerated. Asthma pts with the common comorbidities CRS/NP are often more difficult to treat. Aim: Assess DPL efficacy in asthma pts with CRS/NP. Methods: 382/1902 pts reported CRS/NP medical history. Endpoints: annualized rate of severe exacerbations during the 52-week treatment period and change from BL in FEV₁ at Week 12. Results: CRS/NP pts had higher BL severe exacerbations than non-CRS/NP pts. DPL vs PBO reduced severe exacerbations and improved FEV₁ in difficult-to-treat CRS/NP pts and was equally effective in non-CRS/NP pts (Table). Most common AE, with higher rates in 200/300mg DPL vs PBO, was injection-site reactions (21%/24% vs 6%/14%). Conclusion: DPL improved FEV₁ and reduced severe exacerbations in uncontrolled, moderate-to-severe asthma pts with and without comorbid CRS/NP, and was generally well tolerated.