Abstract
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 (FEV1), and was generally well tolerated in patients with uncontrolled, moderate-to-severe, or oral corticosteroid (OCS)–dependent severe asthma.
The post hoc assessment of dupilumab efficacy versus placebo in P2B and VENTURE in patients stratified by allergic status.
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) FEV1, FEV1/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.
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 FEV1 (P < .01) and FEV1/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.
Dupilumab significantly reduced AER and improved lung function, asthma control, and HRQoL in patients with or without evidence of allergic asthma.