Dupilumab efficacy and safety in patients with allergic bronchopulmonary aspergillosis.

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a complex allergic hypersensitivity reaction to Aspergillus species that can complicate and worsen concomitant asthma and is associated with an intense type 2 immune response in lower airways; there are no approved targeted therapies. To investigate dupilumab, a fully human monoclonal antibody blocking interleukins 4/13 via the shared interleukin 4 receptor alpha, in patients with asthma and ABPA. In this double-blind phase 2 trial, patients with asthma aged ≥12 years who met the clinical criteria for ABPA were randomized to dupilumab (n=35) or placebo (n=27) for 24 to 52 weeks; 37.1% were receiving chronic systemic corticosteroids (SCS). The primary endpoint was change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV₁) at 24 weeks. Additional endpoints included severe respiratory exacerbations and SCS use. At week 24, prebronchodilator FEV₁ was significantly improved with dupilumab versus placebo (least squares mean change, 0.203 L vs 0.002 L; least squares mean treatment difference, 0.201 L; 95% confidence interval [CI], 0.08-0.33; P=0.002). The adjusted annualized severe respiratory exacerbation rate per person-year was 0.695 (95% CI, 0.35-1.36) with dupilumab and 1.551 (95% CI, 0.75-3.22) with placebo, a 55.2% reduction; nominal P=0.0627. At week 24, 71.4% of dupilumab recipients who required SCS at baseline no longer required SCS, compared with 14.3% receiving placebo. Overall safety was consistent with the known dupilumab safety profile. In patients with asthma and ABPA, dupilumab significantly improved lung function compared with placebo, reduced severe respiratory exacerbations, and was well tolerated.