Dupilumab Effective in Reducing Asthma Exacerbations Across Seasons, Study Finds

Patients with type 2 inflammatory asthma, with and without evidence of allergic asthma, experienced reduced exacerbations with dupilumab, regardless of seasons, a study finds.

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This phase 3 randomized, double-blind, placebo-controlled study is published in the Annals of Allergy, Asthma & Immunology.

“In this post hoc analysis, dupilumab vs placebo significantly reduced severe asthma exacerbations in patients with type 2 asthma during QUEST [NCT02414854], independent of seasonality,” wrote the researchers of the study. “These reductions were observed regardless of whether severe exacerbation rates were the highest (winter) or the lowest (summer).”

Because seasonal variability could potentially influence asthma exacerbations, the researchers aimed to evaluate the long-term efficacy of dupilumab in reducing exacerbations across yearly seasons.

Patient’s included in this study were part of a single-arm, open-label extension study that evaluated the long-term safety and efficacy of dupilumab in patients with asthma. Patients had a type 2 phenotype at baseline, as indicated by eosinophils 150 cells/μL or higher, or fractional exhaled nitric oxide 25 ppb or more.

Allergic asthma was defined by baseline immunoglobulin (IgE) of 30 IU/mL or higher plus 1 or more antigen-specific IgE positive results (≥ 0.35 IU/mL) for perennial allergens.

Using this data, the researchers examined the unadjusted annualized exacerbation rate and the proportions of patients who experienced severe asthma exacerbations by month and season for both hemispheres.

In total, the study included 803 patients who received dupilumab and 424 patients who received the placebo, with type 2 asthma. About 51% to 55% of patients across treatment groups were on high-dose inhaled corticosteroids (ICS).

At study baseline, 84% to 85% of patients had an ongoing atopic medical condition and mean (SD) severe exacerbation rates in the previous year were 2.09 (1.94) for dupilumab and 2.25 (1.95) for placebo, respectively. Additionally, most patients (7.2%) were in the Northern Hemisphere, although patient characteristics from the Northern and Southern Hemispheres were generally balanced between the treatment arms.

Moreover, the proportion of patients with dupilumab who experienced 1 or more severe asthma exacerbation compared with placebo was 10% vs 20.8% in spring, 7.3% vs 18.2% in summer, 12.6% vs 22.2% in autumn, and 12% vs 26.4% in winter (P < .001), respectively.

Furthermore, reductions in the proportion of patients who experienced severe exacerbations in those with and without evidence of allergic asthma were like the that of the observed type 2 asthma population. These reductions in severe exacerbations were sustained up to 96 weeks across both hemispheres.

However, the researchers noted some limitations to their study. First, specific IgE was only assessed based on perennial allergens and not seasonal allergens. Because of this, the definitions of allergic asthma were independent of allergen exposure or challenge specific to a particular season. Second, only patients who completed the parent QUEST study were eligible for participation in the open-label extension study and participated on a voluntary basis. Therefore, the researchers acknowledged that this may have led to treatment bias.

Yet, despite these limitations, the researchers believe this study showed dupilumab is effective in reducing severe asthma exacerbations, regardless of seasons.

“The proportion of patients experiencing 1 or more exacerbations declined further during TRAVERSE [NCT02134028] years 1 and 2, when all patients received dupilumab long term,” wrote the researchers. “These patterns were found across subgroups by hemisphere and either exacerbation history, ICS dose, or with or without an allergic phenotype.”

Reference

Peters AT, Sagara H, Corren J, et al. Impact of dupilumab across seasons in patients with type 2, uncontrolled, moderate-to-severe asthma. Annals of Allergy, Asthma & Immunology. Published online November 25, 2023. doi:10.1016/j.anai.2023.11.021