Dupilumab improved mucus burden in adults with moderate-to-severe asthma regardless of their baseline lung function and fractional exhaled nitric oxide (FeNO) scores, according to new data from the phase 4 VESTIGE trial.
In late-breaking data presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago, IL, this week, investigators from VESTIGE reported significantly reduced mucus plug scores and volume from baseline among adult patients with asthma following 24 weeks of dupilumab add-on therapy. The significant benefit was achieved irrespective of patients’ baseline pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) and FeNO levels.
The findings add weight to the prior VESTIGE trial evidence supporting the interleukin 4 and 13 (IL-4, IL-13) targeting biologic’s benefit to airway inflammation and mucus plugging among patients with moderate-to-severe asthma — further emboldening prescribing clinicians to consider add-on dupilumab for adult patients with moderate-to-severe type 2 asthma.
In an interview with HCPLive during CHEST 2025, study author Njira Lugogo, MD, director of the University of Michigan Health’s Pulmonary & Critical Care Medicine Asthma Program, discussed the significance of achieving mucus plus burden relief in this patient population regarding of key risk biomarkers. Lugogo said mucus plugs have become an increasingly apparent issue in patients with uncontrolled asthma — though their presence and impact may still be misunderstood among her peers.
Mucus plugs are highly common in cases of type 2 asthma, and are a consequence of airway mucin MUC5AC cross-linked with Charcot-Leyden crystals (CLCs) and eosinophils producing inflammatory peroxidases that result in “very thick concretion that’s tethered to the airway.”
“They don't respond to inhaled steroids, oral steroids, nor bronchodilators. So, all our current conventional treatments do not get rid of plugs,” Lugogo said.” They make people have lower lung function. You get more air trapping. So, they do have clinical consequences for our patients, and in the context of asthma, about half the patients have mucus plugs.”
Lugogo’s advice for clinicians based on her team’s latest VESTIGE findings is to more formally adopt strategies to identify mucus plugs in patients not improving from their type 2 asthma. Initiating dupilumab has shown these patients can achieve benefit within 4 weeks.
“There's a little more improvement by 26 weeks, but it's a pretty rapid depletion improvement in plugs,” Lugogo said. “And so, you can talk to your patients about this topic, show them the plugs, and let them know with some confidence that if they have plugs, there is likely to be a clinical impact on mucus plug scores, and consequently we would expect improvements in obstruction, symptoms, and so forth.”
Lugogo additionally discussed ongoing research into artificial intelligence (AI) and machine learning to assist in automating mucus plug counting, given the time-laden standard currently at practice. The ultimate goal, she hypothesized, would be to receive automated mucus plug scores post-scan.
“There’s more to come on this topic,” Lugogo said. “I think it's going to continue to grow in terms of interest and in our ability to increase the clinical applicability of mucus plugs.”
References
- Perez De Llano L, Dunican E, Lugogo NL, et al. Dupilumab Reduces Mucus Burden Irrespective of Baseline Respiratory Characteristics in Patients with Uncontrolled Moderate-to-Severe Asthma: Results from the VESTIGE Study. Poster presented at: CHEST Annual Meeting 2025. Chicago, IL. October 19 – 22, 2025.
- Castro M, Papi A, Porsbjerg C, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2025;13(3):208-220. doi:10.1016/S2213-2600(24)00362-X
