PC3021: The Effect of Allergen Sensitization Status on Dupilumab Efficacy in VOYAGE Pediatric Patients with Uncontrolled, Moderate-to-severe Type 2 Inflammatory Asthma

Background: 85% of children with uncontrolled, moderate-to-severe asthma have type 2 (T2) inflammatory asthma (baseline blood eosinophils ≥150 cells/µL or FeNO ≥20 ppb); most of these children exhibit an allergic phenotype. Asthma can lead to severe and/or frequent exacerbations and abnormal lung function. Dupilumab (DPL), a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, key and central drivers of T2 inflammation in multiple diseases. In phase 3 VOYAGE (NCT02948959), add-on DPL vs placebo reduced severe asthma exacerbations and improved lung function in children aged 6 to 11 years with uncontrolled, moderate to severe T2 asthma. Dupilumab has demonstrated an acceptable safety profile. To determine the effect of allergen sensitization, we conducted a post hoc analysis comparing efficacy of DPL vs placebo in non-, monoallergen- and multiallergen-sensitized VOYAGE patients with T2 asthma.

Methods: Children were classified as non- (total serum IgE < 30 IU/mL or no perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline), monoallergen- or multiallergen-sensitized (total baseline serum IgE ≥30 IU/mL in both, and 1 (mono-) or >1 (multi-) aeroallergen-specific IgE ≥0.35 kU/L, respectively). Annualized severe asthma exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) percent predicted forced expiratory volume in 1 second (pre-BD FEV1pp) were compared.

Results: DPL vs placebo significantly reduced AER [95% CI] in monoallergen- (0.105 [0.022–0.511] vs 0.423 [0.114–1.566], relative risk reduction [RRR]: –75.1%; P=0.04) and multiallergen-sensitized (0.246 [0.157–0.385] vs 0.607 [0.391–0.944], RRR: –59.6%; P< 0.001) patients and numerically reduced AER in non-sensitized patients (0.444 [0.243–0.814] vs 0.804 [0.448–1.442], RRR: –44.7%; P=0.13) (Figure). Moreover, DPL vs placebo significantly improved pre-BD FEV1pp in multiallergen-sensitized patients at Weeks 2 (LSMD [95% CI]: 5.3 percentage points [1.4–9.2]; P=0.007), 12 (LSMD [95% CI]: 6.4 percentage points [2.0–10.8]; P=0.005) and 52 (9.0 percentage points [4.0–14.1]; P< 0.001) and monoallergen-sensitized patients at Week 52 (LSMD [95% CI]: 10.1 percentage points [4.2–16.1]; P=0.001).

Conclusion: DPL significantly reduced exacerbations in monoallergen- and multiallergen-sensitized children aged 6 to 11 years with uncontrolled moderate-to-severe asthma and a T2 inflammatory phenotype. Moreover, DPL significantly improved lung function by Week 52 in monoallergen-sensitized patients and as early as Week 2 in multiallergen-sensitized patients.