Dupilumab Efficacy in Patients With Uncontrolled, Moderate-to-Severe Allergic Asthma

IL-4 and IL-13 are drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. Dupilumab blocks the shared receptor component for IL-4 and IL-13, inhibiting subsequent signaling of cytokines which drive type 2 inflammation. This study evaluated the effect of dupilumab on asthma outcome measures in subgroups of patients with asthma.

This study is a post hoc analysis of patients enrolled in a phase 3, randomized, double-blind, placebo-controlled study of efficacy and safety of dupilumab, which enrolled adolescents and adults ≥12 years with physician-diagnosed asthma receiving treatment with a medium-to-high dose inhaled glucocorticoid and up to 2 additional controllers. Allergic asthma criteria included total serum IgE ≥30 IU/mL and ≥1 positive perennial aeroallergen-specific IgE ≥0.35 kU/L. A total of 1902 patients were randomized in a 2:2:1:1 ratio to add-on subcutaneous dupilumab 200 mg (loading dose 400 mg) or 300 mg (loading dose 600 mg) every 2 weeks or matched-volume placebos for 52 weeks. One thousand eighty-three patients met the criteria used to define allergic asthma, whereas 819 patients did not meet these criteria.

Efficacy analyses were performed in the intention-to-treat population of all randomized patients. Evaluated endpoints were annualized severe exacerbation rates, change from baseline in prebronchodilator forced expiratory volume in one second (FEV₁), and change from baseline in 5-item Asthma Control Questionnaire (ACQ-5) score over the treatment period. Dupilumab effects on type 2 inflammation biomarkers including serum total IgE, fractional exhaled nitric oxide (FeNO), and serum thymus and activation-regulated chemokine (TARC) were also assessed in both subgroups.

In the allergic asthma subgroup, dupilumab 200/300 mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (−36.9%/−45.5%), and improved FEV₁ by least-squares mean at week 12 (0.13 L/0.16 L). In the nonallergic asthma subgroup, dupilumab 200/300 mg reduced severe asthma exacerbation rates (−60.0%/−44.6%) and improved FEV₁ by least-squares mean at week 12 (0.14 L/0.09 L). Dupilumab reduced FeNO after 2 weeks of treatment and reduced TARC concentrations versus placebo at 12 weeks in both subgroups. Reductions were sustained throughout the treatment period. Patients with baseline serum total IgE ≥700 IU/mL also benefitted.

Dupilumab reduced severe exacerbations rates, improved FEV_1, improved ACQ-5 scores, and suppressed type 2 inflammatory biomarkers in both subgroups. Severe exacerbation reduction rates and FEV₁ improvements were greater in patients with higher baseline levels of type 2 inflammatory biomarkers.

Although further study is needed in patients <12 years, dupilumab demonstrated efficacy in patients with and without increased expression of specific IgE to aeroallergens, suggesting a common role of IL-4 and IL-13 in airway inflammation in both asthma phenotypes studied. Clinical efficacy in patients with baseline serum total IgE ≥700 IU/mL is encouraging and may offer a viable option for patients who are not candidates for omalizumab.