Dupilumab efficacy and safety in patients with allergic bronchopulmonary aspergillosis.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: In patients with asthma and ABPA, dupilumab significantly improved lung function compared with placebo, reduced severe respiratory exacerbations, and was well tolerated.