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The following is a summary of “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,” published in the February 2025 issue of The Lancet Respiratory Medicine by Castro et al. 

Researchers conducted a retrospective study using functional respiratory imaging to evaluate airway structural and functional changes, with mucus plugging, in response to dupilumab for asthma.  

They assessed adults aged 18–70 years diagnosed with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophil count ≥300 cells/μL and fractional exhaled nitric oxide [FeNO] ≥25 parts per billion [ppb]) on medium-to-high dose inhaled corticosteroids with other controller medications. Participants were randomly assigned (2:1; block size of 6) by interactive voice–web response technology to receive add-on dupilumab 300 mg subcutaneously every 2 weeks or volume-matched placebo for 24 weeks. Randomization was stratified by inhaled corticosteroid dose and region (USA vs non-USA), with participants and investigators masked to group assignment. Primary endpoints were the proportion of individuals with FeNO below 25 ppb at week 24 and percentage change in specific regional airway volumes corrected for lung volume ([s]iV_aw) at total lung capacity (TLC), analyzed in the intention for the treatment. Safety was evaluated in all who received at least 1 dose of the study drug or placebo. 

The results showed that recruitment occurred from July 18, 2020, to January 6, 2023. Participants (mean age 50.4 years [SD 12.6]; 68 [62%] female and 41 [38%] male) were randomly assigned to receive dupilumab 300 mg (n=72) or placebo (n=37). At week 24, more individuals in the dupilumab group had a fractional exhaled  FeNO concentration below 25 ppb (41 [57%] of 72) compared to the placebo group (4 [11%] of 37; odds ratio: 9.8 [95% CI 3.1 to 30.8]; P <0.001). Dupilumab led to a numerical increase in specific regional airway volumes corrected in [s]iV_aw at TLC, but the difference was not significant (least squares [LS] mean percentage change from baseline to week 24: 19.7% [SE 8.1] for dupilumab, −2.0% [11.5] for placebo; LS mean difference vs placebo: 21.8% [95% CI −7.7 to 51.3]; P =0.14). Treatment-emergent adverse events related to the study intervention occurred in 11 (15%) of 72 individuals in the dupilumab group and 4 (11%) of 37 in the placebo group, with no deaths reported. 

Investigators concluded that dupilumab reduced airway inflammation and mucus plugging with improvement in lung function and asthma control, demonstrating the potential of imaging technology to inform clinical decisions for patients with moderate-to-severe type 2 asthma. 

Source: thelancet.com/journals/lanres/article/PIIS2213-2600(24)00362-X/abstract