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Dupilumab Cuts Lung Inflammation, Breaks Up Mucus Plugs in Asthma Patients

— In VESTIGE trial, IL-4/IL-13 blocker also improved airway volumes and airflow

MedpageToday

WASHINGTON -- Dupilumab (Dupixent) reduced airway inflammation and increased lung capacity in patients with uncontrolled, moderate-to-severe asthma, while also reducing troublesome mucus plugs, a multinational postmarketing study showed.

In the randomized study, treatment with dupilumab led to significant reductions in airway inflammation at 24 weeks, with 57% achieving a fractional exhaled nitric oxide (FeNO) level below 25 ppb versus 11% of those assigned to placebo (P<0.001), reported Njira Lugogo, MD, of the University of Michigan in Ann Arbor, at the American Academy of Allergy, Asthma & Immunology annual meeting.

The study's second primary endpoint showed that dupilumab numerically improved lung volume measures at this time point as well. The least squares (LS) mean percentage change in untrimmed distal airway volumes corrected for lung volume (siVAW) at total lung capacity increased by 19.73% from baseline with the interleukin (IL)-4/IL-13-blocking antibody, as compared with a 2.04% decrease from baseline in the placebo group.

Additionally, global mucus scores numerically improved in the dupilumab group, with a LS mean decline of -3.48 versus an increase of 1.44 in the placebo group per University of California San Francisco criteria (nominal P<0.001). The scoring system relies on CT imaging to determine how many of a patient's lung segments are obstructed with mucus plugs, with higher scores associated with lower lung function likely due to occlusion of the airway, said Lugogo.

Present in about two-thirds of patients with severe asthma, mucus plugs can and don't respond to high doses of inhaled or oral corticosteroids, Lugogo explained.

"We're not talking about sputum that patients can easily cough up -- mucus plugs are very hard to cough up," she told MedPage Today. "They are thick, gelatinous, and cannot be expectorated very easily. Mucus plugs tend to occlude the airway and are stable over time, generally remaining in the same sub-segment over years."

Lugogo said she was surprised at how quickly mucus scores improved with dupilumab, with notable reductions as early as week 4. "It happened quite early. I would have thought a mucus plug takes forever to get rid of," she said.

The phase IV trial utilized novel functional respiratory imaging to evaluate dupilumab's effects on airway inflammation, functional or structural changes in airway volume, and mucus plugs. Patients underwent CT scans at baseline that were repeated at 4- and 24-week visits.

"By using functional respiratory imaging to produce 3D visualizations, we were able to track asthma disease progression and the biologic's efficacy with much greater accuracy than with traditional methods like spirometry," Lugogo said in a .

Patients in the study were randomized 2:1, with 72 individuals assigned to dupilumab (either a 600-mg subcutaneous or 4-mL subcutaneous loading dose followed by a 300-mg or 2-mL dose every 2 weeks) and 37 to volume-matched placebo.

Enrollment criteria included moderate-to-severe asthma with an eosinophilic phenotype or that was oral corticosteroid dependent: an Asthma Control Questionnaire (ACQ)-5 score of 1.5, a pre-bronchodilator forced expiratory volume in 1 second (FEV1) 80% of predicted value, at least one exacerbation in the prior year, a blood eosinophil count of 300 cells/μL, and a FeNO level of 25 ppb or above.

Overall, the average patient age was about 50 years, over 60% were women, and about 90% were white, with nearly two-thirds enrolled from Eastern Europe.

Mean baseline measures between the dupilumab and placebo groups, respectively, were as follows: FeNO level (63.1 vs 52.7 ppb), pre-bronchodilator FEV1 (1.850 vs 1.896 L), siVAW at total lung capacity (1.91 L in both groups), airway resistance (0.172 vs 0.125 kPa*s/L), mucus score (7.2 vs 6.9).

The study's primary endpoints were the proportion of patients achieving a FeNO level below 25 ppb and the percent change from baseline in siVAW at 24 weeks. Secondary endpoints included changes in mucus scores and the percent change from baseline in airway resistance (siRAW) at total lung capacity at 24 weeks.

For siRAW, the LS mean percentage change decreased by 25.5% in the dupilumab group and increased by 34.3% in the placebo group.

Treatment-emergent adverse events (TEAEs) were reported in 43% of the dupilumab group and 57% of the placebo group, with 15% and 11% deemed related to the study intervention. Severe TEAEs occurred in 4.2% and 2.7%, respectively.

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    Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology.

Disclosures

VESTIGE was supported by Sanofi and Regeneron Pharmaceuticals.

Lugogo disclosed relationships with Regeneron, Sanofi, Amgen, AstraZeneca, Avillion, Genentech, Gossamer Bio, GSK, Teva, and Novartis. Some co-investigators are employees of Sanofi or Regeneron.

Primary Source

American Academy of Allergy, Asthma & Immunology

Lugogo N "Evaluating the effect of dupilumab on type 2 airway inflammation and mucus plugging in patients with uncontrolled moderate-to-severe asthma: the VESTIGE trial" AAAAI 2024. Abstract L24.