Dupilumab reduces asthma exacerbations in patients with, without fungal sensitization
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Dupilumab treatment reduced asthma exacerbations among patients both with and without evidence of fungal sensitization on medium- or high-dose inhaled corticosteroids, according to a post hoc analysis of the LIBERTY ASTHMA QUEST study.
LIBERTY ASTHMA QUEST was a randomized, double-blind, phase 3 study that evaluated add-on dupilumab (Dupixent, Sanofi/Regeneron) 200 mg/300 mg every 2 weeks compared with placebo in patients with moderate to severe asthma. Dupilumab reduced asthma exacerbations and improved pre-bronchodilator FEV1 among those with uncontrolled, moderate to severe asthma. For the post hoc analysis, researchers assessed dupilumab treatment efficacy in patients with type 2 asthma with and without fungal sensitization.
“Up to 30% of asthma patients show evidence of fungal sensitization characterized by increased asthma severity, a type 2 response, and potential progression to bronchiectasis/fibrosis,” Jonathan Corren, MD, an allergist-immunologist at the David Geffen School of Medicine at UCLA, and colleagues wrote in an abstract presented at the European Academy of Allergy & Clinical Immunology Conference. “Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers for type 2 inflammation.”
The post hoc analysis included a subpopulation of patients on medium- or high-dose inhaled corticosteroids (ICS) at baseline with fungal sensitization specific to Alternaria alternata, A. fumigatus and Cladosporium herbarum more than 0.35 IU/mL or without fungal sensitization.
The primary endpoints were the annualized rate of severe asthma exacerbations and change in pre-bronchodilator FEV1 from baseline over 52 weeks.
Of the 1,505 patients in the LIBERTY ASTHMA QUEST study, 282 had fungal sensitization at baseline; of those, 155 were on high-dose ICS (placebo, 63; dupilumab, 92) and 127 were on medium-dose ICS (placebo, 45; dupilumab, 82). There were 630 patients without fungal sensitization who were on high-dose ICS (placebo, 218; dupilumab, 412) or medium-dose ICS (placebo, 197; dupilumab, 396) at baseline.
Compared with placebo, dupilumab treatment significantly reduced the annualized rate of severe asthma exacerbations in patients with fungal sensitization on medium-dose ICS. Patients with fungal sensitization who were on high-dose ICS and received dupilumab had a 28% reduction in the annualized rate of severe exacerbations, according to the results.
Among those without fungal sensitization, dupilumab also significantly reduced the annualized rate of severe asthma exacerbations regardless of ICS dose, according to the abstract.
At week 12, pre-bronchodilator FEV1 was 0.12 L for those with fungal sensitization on high-dose ICS (P = .0656), 0.15 L for those without fungal sensitization on high-dose ICS (P < .0001), 0.13 L for those with fungal sensitization on medium-dose ICS (P = .0721) and 0.18 L for those without fungal sensitization on medium-dose ICS (P< .0001), according to the results.
Editor's note: This article was updated on July 6, 2022, to clarify that dupilumab was given every 2 weeks in patients with moderate to severe asthma.