Dupilumab Efficacy in Patients With Uncontrolled or Oral Corticosteroid-Dependent Allergic and Nonallergic Asthma.

Background: Type 2 cytokines IL-4/IL-5/IL-13 play an important role in pathogenesis of type 2 conditions, including asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In phase 2b (P2B) (NCT01854047) and phase 3 VENTURE (NCT02528214), dupilumab reduced annualized severe exacerbation rates (AER), improved forced expiratory volume in 1 second (FEV), and was generally well tolerated in patients with uncontrolled, moderate-to-severe, or oral corticosteroid (OCS)-dependent severe asthma.

Objective: The post hoc assessment of dupilumab efficacy versus placebo in P2B and VENTURE in patients stratified by allergic status.

Methods: Allergic asthma was defined as total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline. AER, prebronchodilator (BD) FEV, FEV/forced vital capacity (FVC) ratio, asthma control (5-item Asthma Control Questionnaire), health-related quality of life (HRQoL; Asthma Quality of Life Questionnaire), type 2 biomarkers, specific IgE, and OCS reduction (VENTURE only) were assessed.

Results: In patients with allergic asthma, dupilumab (P2B: pooled 200/300 mg; VENTURE: 300 mg) every 2 weeks versus placebo reduced AER (P2B: -60%, P < .01; VENTURE: -72%, P < .001), and, in P2B, increased pre-BD FEV (P < .01) and FEV/FVC (P < .05). In both studies, dupilumab significantly improved asthma control and HRQoL and reduced most type 2 biomarkers. Dupilumab significantly reduced OCS use in VENTURE. Similar benefits were observed in patients without evidence of allergic asthma.

Conclusions: Dupilumab significantly reduced AER and improved lung function, asthma control, and HRQoL in patients with or without evidence of allergic asthma.