Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1 ) and quality-of-life measures and was generally well tolerated in patients with uncontrolled, persistent (phase 2b) or moderate-to-severe (phase 3) asthma. Methods: In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV1 and asthma control (5-item Asthma Control Questionnaire [ACQ-5]) were analyzed. Results: In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w versus placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P<.001), respectively, except in patients with ≥300 eosinophils/µL in phase 2b study (24%/50% (P=.52/.15). Across subgroups, pre-BD FEV1 improved by 0.18-0.22 L/0.19-0.24 L (all P<.05) and 0.23-0.36 L/0.15-0.25 L (all P<.01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P<.05) and 0.38-0.50/0.24-0.30 (all P<.05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥25 ppb (0.41; P=.09). Dupilumab was also effective in patients taking medium-dose ICS. Conclusion: Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.