Dupilumab lowers type 2 airway inflammation, mucus plugs in uncontrolled asthma
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Key takeaways:
- Dupilumab for uncontrolled asthma improved mucus plugging and airway inflammation, volume and resistance.
- Drug safety in this trial was in line with dupilumab’s known safety profile.
WASHINGTON — Among adults with uncontrolled moderate to severe asthma and high type 2 inflammation measures, 24-week dupilumab lowered inflammation and mucus plug scores, according to study results.
These data on dupilumab (Dupixent; Sanofi, Regeneron) were presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
“These findings provide additional evidence that dupilumab can significantly reduce airway inflammation, reduce mucus plugging and improve airway volume and flow in adults with uncontrolled moderate to severe asthma — all of which are critical in helping patients achieve optimal control of their asthma,” Njira L. Lugogo, MD, MS, asthma program director of the division of pulmonary and critical care medicine at University of Michigan, told Healio.
In a multinational, randomized, double-blind, placebo-controlled imaging phase 4 trial (VESTIGE), Lugogo and colleagues assessed 109 adults with uncontrolled moderate to severe asthma, blood eosinophil counts of 300 cells/μL or higher and fractional exhaled nitric oxide (FeNO) of 25 ppb or higher to determine how dupilumab impacts FeNO and airway volumes corrected for lung volume at total lung capacity after 24 weeks.
Of the total cohort, 72 patients received a 600 mg loading dose of dupilumab followed by 300 mg dupilumab every 2 weeks, whereas the remaining 37 patients received placebo.
Researchers observed changes in FeNO, airway volume, specific airway resistance and mucus plugging in both groups through functional respiratory imaging (FRI).
“I believe the images obtained from FRI would be meaningful to patients since they allow us to actually visualize the therapeutic effects in the lungs and, as we all know, a picture is worth a thousand words,” Lugogo said.
Between the dupilumab group and the placebo group, significantly more patients receiving dupilumab had a FeNO less than 25 ppb at week 24 (56.9% vs. 10.8%), signaling lower type 2 airway inflammation. These patients also had significantly higher odds for this outcome (OR = 9.81; 95% CI, 3.13-30.82), according to researchers.
Compared with baseline measures, airway volume improved to a greater degree in the dupilumab group vs. the placebo group at week 24 (least squares mean difference, 21.76%), but this percent change was not significant.
Patients receiving dupilumab also had lower airway resistance at 24 weeks from baseline than patients receiving placebo (median treatment difference, –59.8%), and this demonstrates improved lung function, researchers wrote.
Lastly, mucus plug scores significantly declined by week 24 among patients receiving dupilumab compared with patients receiving placebo (least squares mean difference, –4.92), which Lugogo said was surprising.
“Mucus plug scores improved much faster with dupilumab than I would have expected,” Lugogo told Healio. “Mucus plugs are typically stable and can be present in the same part of the airway for years and are generally hard to resolve. Therefore, seeing the plugs improve by the time the first imaging was obtained was truly noteworthy.”
Researchers did not observe any differences between safety results of dupilumab from this trial and the drug’s known safety profile. Adverse events that occurred in 1% or more of patients receiving dupilumab included injection site reaction, COVID-19, vascular disorders, cardiac disorders and infections and infestations.
“The models created in the VESTIGE study utilized FRI, which allowed us to track disease progression in the lungs with much greater specificity and detail than traditional methods,” Lugogo said. “I believe that by continuing the use of these novel imaging technologies with future studies — in asthma and otherwise — we can more accurately illustrate the effect of biologics on respiratory health.”
References:
- Castro M, et al. J Allergy Clin Immunol. 2024;doi:10.1016/j.jaci.2023.11.879.
- Dupixent continues scientific leadership with late-breaking results showing reduced airway inflammation and mucus plugging in adults with uncontrolled moderate to severe asthma. https://www.sanofi.com/en/media-room/press-releases/2024/2024-02-24-13-00-00-2834714. Published Feb. 24, 2024. Accessed March 1, 2024.