Dupilumab improves asthma outcomes in allergic and nonallergic asthma
Published: December 23, 2022
Asthma is a heterogeneous disease, including allergic asthma, characterized by elevated levels of circulating total and allergen-specific Immunoglobulin E (IgE), and non-allergic asthma. The cytokines interleukin-(IL)-4 and IL-13 play key roles in type 2 inflammation which is a hallmark of allergic airway disease and are implicated in numerous allergic diseases including allergic asthma. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, thus inhibiting their signaling. In the phase 2b study (NCT01854047), dupilumab vs placebo reduced the risk of severe asthma exacerbations and improved lung function in patients with uncontrolled, moderate-to-severe asthma. In the phase 3 VENTURE study (NCT02528214), dupilumab significantly reduced oral corticosteroid use while simultaneously reducing the risk of severe asthma exacerbations and improving lung function in patients with oral corticosteroid-dependent severe asthma.
A previous post hoc analysis of the phase 3 dupilumab QUEST study found that dupilumab significantly reduced the risk of severe asthma exacerbations and improved lung function and asthma control in moderate-to- severe asthma patients with or without evidence of allergic asthma. In a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Brusselle and colleagues performed a post hoc analysis to investigate the efficacy of dupilumab in patients with moderate-to-severe uncontrolled asthma from the phase 2b study and steroid-dependent asthma from the phase 3 VENTURE study, with or without evidence of allergic asthma. For the analysis, allergic asthma was defined by elevated total IgE levels and elevated levels of allergen-specific IgE to at least 1 perennial allergen at study baseline.
In this analysis, treatment with dupilumab significantly reduced asthma exacerbations and improved lung function, asthma control, and health-related quality of life in patients with or without evidence of allergic asthma. These improvements were observed as early as Week 2 of treatment and continued throughout the length of the study. Dupilumab treatment also reduced biomarkers of type 2 inflammation, including total and allergen-specific IgE levels, consistent with dupilumab’s mechanism of action. Together these results showed that dupilumab was effective in treating patients with moderate-to-severe and oral corticosteroid-dependent asthma, with and without evidence of allergic asthma. These results reinforce the role of IL-4 and IL-13 in allergic and non-allergic asthma and provide additional evidence related to the use of dupilumab to treat OCS- dependent asthma with or without evidence of an allergic phenotype.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.