Dupilumab is effective in patients with uncontrolled, moderate-to-severe allergic asthma
Published online: September 12, 2019
The term asthma covers a broad spectrum of disease phenotypes, with the most prevalent type of uncontrolled, persistent asthma being “type-2 high” where type 2 cytokines, such as interleukin (IL)-4 and IL-13, play key roles in driving airway inflammation. This includes patients with allergic asthma, which is characterized by high levels of serum total IgE and specific IgE to airborne substances. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component of IL-4 and IL-13, thus inhibiting these key drivers of type 2 inflammation.
In the phase 3 LIBERTY ASTHMA QUEST study, dupilumab 200 mg and 300 mg every 2 weeks vs placebo reduced severe asthma exacerbations and improved lung function and quality of life in patients with uncontrolled, moderate-to-severe asthma. In a recently published paper in The Journal of Allergy and Clinical Immunology: In Practice, Corren and colleagues describe a post hoc analysis of this trial in which the efficacy of dupilumab was evaluated in subgroups of patients with and without evidence of allergic asthma.
At baseline, patients with evidence of allergic asthma were generally younger, with earlier asthma onset, and more patients had comorbid conditions than those with non-allergic asthma. Dupilumab treatment reduced the number of severe exacerbations and improved lung function and asthma control in patients both with and without evidence of allergic asthma, with greater efficacy observed in patients with elevated type 2 biomarkers at baseline. These improvements were observed as early as 2 weeks after treatment began and were sustained throughout the 52-week treatment period. Markers of type 2 inflammation, including IgE, were also reduced by dupilumab in both patient subgroups, consistent with its mechanism of action. These benefits extended to patients with serum total IgE levels greater than 700 IU/mL, for whom anti-IgE therapies are not indicated in the USA.
Dupilumab was effective in the treatment of patients with evidence of allergic asthma as well as those who did not meet the criteria for allergic asthma. The findings from this study support the critical roles of IL-4 and IL-13 in IgE- and non–IgE-mediated inflammation in asthma and show that dupilumab is an effective treatment for both allergic and non-allergic asthma phenotypes.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.