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 (FEV(1)) and quality of life measures, and it 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 FEV(1) 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 vs 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 = .52/0.15). Across subgroups, pre‐BD FEV(1) 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.