Inflammation, mucus plugging improve by 4 weeks with dupilumab

Key takeaways:

• The treatment group was four times more likely to achieve FeNO of less than 25 ppb by week 4 than the placebo group.
• Improvements also included mucus plugging scores and airway resistance.

Patients with asthma on dupilumab saw reduced airway inflammation and mucus plugging beginning at 4 weeks with steady improvements through 24 weeks, according to a study presented at the European Respiratory Society International Congress.

“Chronic airway inflammation is associated with increased mucus production and airway remodeling, but current inhaled treatment does not fully address these alterations,” Alberto Papi, MD, PhD, professor of respiratory medicine at the University of Ferrara in Italy, told Healio.

Mucus plugging blocks the airways, makes breathing difficult, and can lead to structural changes in the airways and lungs, Papi said.

“We wanted to understand how dupilumab might impact these underlying biological changes in the airways and lungs,” he said.

The VESTIGE study included patients aged 21 to 70 years (62% women) with uncontrolled, moderate to severe asthma. Most patients were white, 10% were Asian and 1% were Black, Papi said.

At baseline, patients had blood eosinophil counts of 300 cells/µL or higher and fractional exhaled nitric oxide counts of 25 ppb or higher. They also had five-question Asthma Control Questionnaire scores of 1.5 or higher, pre-bronchodilator percent-predicted FEV₁ scores of 80% or lower, and one exacerbation or more in the previous year.

Treatment included 300 mg of dupilumab (Dupixent; Regeneron, Sanofi; n = 72) or placebo (n = 37) every 2 weeks for 24 weeks.

FeNO was four times (95% CI, 1.7-9.6) more likely to fall below 25 ppb by 4 weeks in the dupilumab group compared with the placebo group, with 40 patients in the dupilumab group and eight in the placebo group reaching this goal.

At 24 weeks, the dupilumab group was 9.8 times (95% CI, 3.1-30.8) more likely to have FeNO less than 25 ppb than the placebo group, with 41 patients in the dupilumab group and four in the placebo group reaching this goal.

Percent changes in least square mean (LSM) from baseline to 4 weeks in quantitative CT airway volumes at total lung capacity (TLC) included 7.8 (standard error [SE], 24.1) for the placebo group (n = 33) and 32 (SE, 17.1) for the dupilumab group (n = 66). The least square mean difference between the groups was 24.2 (standard error, 29.4; 95% CI, –34.11 to 82.56).

At week 24, percent changes in LSM from baseline in quantitative CT airway volumes at TLC included –2 (SE, 11.5) for the placebo group (n = 30) and 19.7 (SE, 8.1) for the dupilumab group (n = 63) with an LS mean difference of 21.8 (95% CI, –7.7 to 51.3) between the groups.

Percent changes in LSM airway resistance at TLC at week 4 included 28.7 (SE, 20.8) for the placebo group (n = 33) and 11.7 (SE, 14.8) for the dupilumab group (n = 66), with an LSM difference between the groups of –17 (95% CI, –67 to 33.1).

At week 24, percent changes in LSM airway resistance included 90.3 (SE, 32.5) for the placebo group (n = 30) and 36.9 (SE, 22.6) for the dupilumab group (n = 63), with an LSM difference of –53.5 (95% CI, –132.1 to 25.2) between the groups.

Median percent changes in airway resistance at TLC at week 4 included –16% (Q1-Q3, –55% to 45.6%) for the dupilumab group and 6.1% (Q1-Q3, –40.1% to 54.6%) for the placebo group.

At week 24, these median percent changes in airway resistance in TLC included –25.5% (Q1-Q3, –50.4% to 58.6%) for the dupilumab group and 34.3% (Q1-Q3, –38.2% to 142.7%) for the placebo group.

The LSM difference in mucus scores at week 4 was –3 (SE, 0.7; 95% CI, –4.39 to –1.63) between the dupilumab (n = 72) and placebo (n = 37) groups. At week 24, the LSM difference between the groups was –4.92 (SE, 0.8).

“Patients receiving dupilumab were 9.8 times more likely to achieve fractional exhaled nitric oxide, an airway biomarker of inflammation, of less than 25 ppb compared with placebo,” Papi added.

Based on these findings, the researchers said that dupilumab reduced airway inflammation and mucus plugging and classified further improvements beyond week 4 as rapid and steady.

“We have CT scans of patients’ lungs that visually show where in the airways dupilumab is improving airflow and the differences from placebo at both 4 and 24 weeks,” Papi said. “It’s quite striking to see.”

These findings also help physicians understand how dupilumab can improve the signs and symptoms of asthma, he continued.

“With the knowledge that dupilumab can reduce inflammation and increase airflow to the lungs by decreasing mucus within 4 weeks, doctors can expect some patients to start experiencing improvement in their asthma fairly quickly once they start treatment, and these improvements may continue over time,” Papi said.

The study is complete, Papi further said, but the researchers’ work persists.

“We will continue to analyze the results to gain a complete understanding of how dupilumab can impact lung biology with the insights from this novel imaging technology,” he said.