麻豆传媒

WASHINGTON -- Adding dupilumab (Dupixent) to a medium-dose inhaled corticosteroid (ICS) routine helped lower asthma exacerbations and improved both lung function and asthma control, according to a post-hoc analysis of the LIBERTY ASTHMA QUEST trial.

When compared to high-dose ICS treatment paired with a placebo, the monoclonal antibody with medium-dose ICS treatment reduced severe asthma exacerbations by 70% (0.273 vs 0.899 per year, P<0.0001), reported William Busse, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, at the American Academy of Allergy, Asthma and Immunology annual meeting.

The proportion of patients who achieved asthma control increased incrementally in both groups over the course of the trial, but patients on dupilumab consistently outperformed their high-dose ICS counterparts:

• Week 12: 64% vs 42% (OR 2.27, 95% CI 1.65-3.13)
• Week 24: 67% vs 45% (OR 2.29, 95% CI 1.65-3.18)
• Week 52: 71% vs 51% (OR 2.26, 95% CI 1.58-3.24)

The lower exacerbation rate and better symptom control with the medium-dose inhaled steroids and biologic combined indicate that "high-dose inhaled steroids are not really all that specific for the inflammatory component relating to disease expression," Busse said during the presentation.

Busse stressed to 麻豆传媒 that there are a multitude of facets to consider when examining asthma treatments, including lung function improvements, patient quality of life, side effects, and more -- and dupilumab meets several of those criteria.

"I think the surprising data is that it works, and the longer you take it, the better it is," he said. "Also, if you start to look at data for remission, people are finding a greater frequency of meeting criteria for remission."

The trial's primary aim had been to show the impact of add-on dupilumab compared with placebo, with randomization stratified in part based on inhaled glucocorticoid dose (medium or high). Background asthma-controller medications were to be maintained at the stable baseline dose.

Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, met the primary endpoint with a 47.7% lower annualized rate of severe asthma exacerbations and 0.32 L greater absolute change from baseline to week 12 in forced expiratory volume in 1 second (FEV₁) before bronchodilator use as compared with placebo.

Busse's group delved into comparison of background corticosteroid with the post hoc analysis.

The trial's 1,902 patients received inhaled corticosteroids at a medium dose (500-1,000 µg/day) or a high dose (>1,000 µg/day) with additional long-acting β2-agonist medication and could have a third controller at the time of baseline measurements. The analysis included only the 513 patients who received a medium-dose ICS with 200/300 mg add-on of dupilumab every 2 weeks and the 287 patients who received a high-dose ICS with a volume-matched placebo.

Asthma control was assessed via the five-item Asthma Control Questionnaire, with control defined as a score of less than 1.5. Severe exacerbation rates and least squares (LS) mean differences from baseline in pre-bronchodilator FEV₁ were also measured.

At the time of baseline measurements, patients in the high-dose ICS group had an average FEV₁ of 1.71 while patients in the medium-dose ICS plus dupilumab group had an average FEV₁ of 1.91. Differences in LS mean change in FEV₁ from baseline significantly favored the dupilumab-treated patients at various time points and at the conclusion of the 52-week trial (P<0.0001 for all):

• 2 weeks: 0.11 for high-dose ICS and 0.31 for medium-dose ICS and dupilumab patients
• 12 weeks: 0.22 vs 0.37
• 24 weeks: 0.19 vs 0.38
• 52 weeks: 0.18 vs 0.41

In order to be included in the study, patients ages 12 and older needed to have uncontrolled type 2 asthma (here defined as a blood eosinophil count of 150 or more cells/mL or a fractional exhaled nitric oxide of 20 or greater ppb at baseline) and needed to have experienced one or more asthma exacerbations within the year before enrollment in the study.

Busse cautioned that these findings were the result of a post-hoc analysis of a population that wasn't randomized between these two treatment groups specifically, which might potentially limit the findings.

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