Efficacy of dupilumab in patients with uncontrolled, moderate‐to‐severe asthma with fungal sensitization

BackgroundFungal sensitization (FS) exacerbates asthma in patients who have elevated type 2 inflammatory response. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)‐4 and IL‐13, key and central drivers of type 2 inflammation in multiple diseases.ObjectiveThis post hoc analysis, funded by the manufacturers of dupilumab, was conducted to assess dupilumab efficacy in patients from the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) and TRAVERSE open‐label extension (NCT02134028) study who had uncontrolled, moderate‐to‐severe asthma with type 2 inflammatory phenotype (defined as blood eosinophil count ≥150 cells/μL or FeNO ≥25 ppb) and with FS (defined as IgE specific to Alternaria alternata, Aspergillus fumigatus or Cladosporium herbarum >0.35 IU/mL).MethodsWe evaluated annualized rate of severe exacerbations (AER), change from baseline in pre‐bronchodilator (BD) forced expiratory volume in 1 s (FEV1), asthma control (per 5‐item Asthma Control Questionnaire [ACQ‐5]) and biomarker levels (blood eosinophil count, fractional exhaled nitric oxide [FeNO], total IgE, fungal‐specific IgEs, thymus and activation‐regulated chemokine [TARC] and eotaxin‐3).ResultsDupilumab vs. placebo reduced AER, improved pre‐BD FEV1 and asthma control (ACQ‐5), and reduced serum IgE levels, blood eosinophil count, TARC, eotaxin‐3 and FeNO in patients both with and without FS after 52 weeks of treatment in QUEST. Reductions in asthma exacerbation rates and improvements in all other variables were sustained over the TRAVERSE open‐label extension study.ConclusionDupilumab demonstrated efficacy during prolonged treatment in patients with uncontrolled, moderate‐to‐severe asthma with FS.