Dupilumab Improves Small Airway Dysfunction in People With Type 2 Asthma

Dupilumab improved small airway dysfunction (SAD) in people with type 2 high moderate-to-severe asthma, possibly explaining improvements in disease control.1

These findings, from the phase 4 VESTIGE study (NCT04400318), will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Brian Lipworth, MD, Professor of Allergy and Pulmonology at University of Dundee.

“SAD measured by airway oscillometry is related to type 2 inflammation and poor asthma control. Here, we present a post hoc analysis of the phase 4 VESTIGE study evaluating the effects of dupilumab using airway oscillometry,” Lipworth and colleagues wrote.1

The VESTIGE study enrolled adult patients with uncontrolled type 2 high moderate-to-severe asthma that were randomized to receive dupilumab 300 mg (n = 72) or placebo (n = 37) every 2 weeks for 24 weeks. The study’s endpoints were peripheral airway resistance as heterogeneity between 5 and 20 Hz (R5–R20), peripheral compliance as reactance area (AX) using airway oscillometry (with Thorasys Tremoflo®), and the proportion of patients receiving dupilumab who improve from baseline exceeding the biological variability (BV) for R5–R20 ≥0.04 kPa/L/s and AX ≥0.39 kPa/L compared with placebo.1

The investigators found that patients that received dupilumab experienced significant improvements in SAD as measured by peripheral airway resistance and compliance. The dupilumab group had significantly lowered R5–R20 (least squares difference mean [LSM], −0.06 kPa/L/s [95% CI, −0.10 to −0.02]; P <.01) and AX (LSM, −1.43 kPa/L [95% CI, −2.45 to −0.40]; P <.01) than the placebo group. The dupilumab group was also 73% more likely to improve R5–R20 exceeding BV, with an odds ratio [OR] of 3.7 (95% CI, 1.4-9.7; P <.01) compared to the placebo group, and 57% more likely to improve AX exceeding BV, with an OR of 2.35 (95% CI, 1.0, 5.5; P <.05) compared to the placebo group.1

Other recent research on asthma found that inhaled triple therapy (ITT), despite being well known to decrease exacerbation rate and improving lung function for patients with asthma, was still not widely used by clinicians due to uncertainty in implementing it into patients’ treatment regimens.2

“The impact of ITT, nowadays recommended for moderate to severe asthma not adequately controlled by at least average doses of inhaled corticosteroids (ICS) combined with long-acting beta-agonists (LABA), remains to be quantified and is an area of active investigation due to its clinical and management implications. In conclusion, the survey identifies certainties and uncertainties among clinicians regarding the use of triple therapy in clinical practice, highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice,” Bagnasco and colleagues concluded.2

REFERENCES

1. Lipworth B, Saralaya D, Zhang M, et al. Dupilumab Produces Clinically Relevant Improvement in Small Airway Dysfunction in Patients With Moderate-to-Severe Asthma: Results From the Phase 4 VESTIGE Study. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 936.

2. Bagnasco D, Ansotegui I, Baiardini I, et al. Triple inhaled therapy in asthma: Beliefs, behaviours and doubts. Pulm. Pharmacol. Ther. 2024, 102333(87). doi: 10.1016/j.pupt.2024.102333