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January 10, 2023
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Dupilumab reverses persistent airflow obstruction among patients with asthma

Fact checked byKristen Dowd
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Dupilumab facilitated the reversal of persistent airflow obstruction and improved clinical outcomes among patients with uncontrolled moderate to severe asthma, according to a post-hoc analysis in Annals of Allergy, Asthma & Immunology.

The monoclonal antibody also significantly improved clinical outcomes among patients who did not have persistent airflow obstruction (PAO), Nicola A. Hanania, MD, MS, professor of pulmonary and critical care medicine at Baylor College of Medicine, and colleagues wrote.

Percentages of patients with PAO and eosinophils greater than or equal to 300 cells/microliter and FeNO greater than or equal to 25 ppb at baseline achieving post-bronchodilator FEV1/FVC ratios of 0.7 by week 52.
Data were derived from Hanania NA, et al. Ann Allergy Asthma Immunol. 2022;doi:10.1016/j.anai.2022.10.018.

The LIBERTY ASTHMA QUEST phase 3 randomized, double-blind study showed 200 mg and 300 mg dupilumab (Dupixent, Sanofi Genzyme/Regeneron) every 2 weeks for 52 weeks appeared safe and effective vs. matched placebo among 1,902 patients aged 12 years and older with uncontrolled asthma.

The cohort included 1,039 (55%) with PAO, defined as a post-bronchodilator ratio of FEV1 to forced vital capacity (FVC) of 70% or less at baseline. These patients included 685 treated with dupilumab and 354 treated with placebo.

Of patients with PAO, 80% treated with dupilumab and 85% on placebo had elevated type 2 inflammatory biomarkers (eosinophil counts 150 cells/µL or fractional exhaled nitrous oxide 25 ppb), and 32% of those on dupilumab and 33% of those on placebo had even higher elevated type 2 inflammatory biomarkers (eosinophil counts least 300 cells/µL and FeNO 25 ppb).

Lung function

As early as week 2, dupilumab significantly improved pre-bronchodilator FEV1 in patients with and without PAO at baseline compared with placebo.

Specifically, patients with PAO and elevated type 2 biomarkers had a least squares (LS) mean difference of 0.17 L (95% CI, 0.11-0.22) at week 12 and 0.21 L (95% CI, 0.15-0.27) at week 52.

These figures increased to 0.32 L (95% CI, 0.23-0.42) at week 12 and 0.42 L (0.32-0.52) at week 52 for patients higher elevated type 2 biomarkers.

Researchers noted similar improvements, sustained through 52 weeks, in post-bronchodilator FEV1 with dupilumab vs. placebo among patients with elevated type 2 biomarkers who did and did not have PAO at baseline.

PAO

Researchers also observed reversal of PAO — defined as a post-bronchodilator FEV1/FVC ratio of 0.7 or greater — at week 2 among 23.6% of those on dupilumab vs. 13.4% of those on placebo and elevated type 2 biomarkers at baseline, with corresponding figures of 32.5% vs. 18.3% for patients with higher elevated type 2 biomarkers.

At week 52, these percentages increased to 31.1% vs. 15.8% for patients with elevated type 2 biomarkers, and to 44.4% vs. 16.5% for patients with higher elevated type 2 biomarkers.

Overall, dupilumab significantly improved the probability of reversing PAO status vs. placebo among patients with elevated type 2 biomarkers (HR = 1.616; 95% CI, 1.272-2.052) and higher elevated type 2 biomarkers (HR = 1.813; 95% CI, 1.291-2.546).

Exacerbations, quality of life

Dupilumab reduced the annualized rate of severe exacerbations among patients with PAO and elevated type 2 biomarkers (RR = 0.411; 95% CI, 0.327-0.516) and higher elevated type 2 biomarkers (RR = 0.252; 95% CI, 0.178-0.356).

Based on Asthma Quality of Life Questionnaire global scores, dupilumab improved health-related quality of life compared with placebo for patients with and without PAO.

Specifically, patients with elevated type 2 biomarkers experienced LS mean differences of 0.27 (95% CI, 0.13-0.4) at week 12 and 0.39 (95% CI, 0.24-0.54; P < .0001) at week 52 compared with placebo.

Among patients with PAO and higher elevated type 2 biomarkers, the LS mean differences between dupilumab and placebo were 0.41 (95% CI, 0.19-0.63) at week 12 and 0.61 (95% CI, 0.37-0.86) at week 52, with similar results for subgroups that did not have PAO (P < .05 for all).

With improvements across all subgroups and particularly for patients with higher elevated biomarkers of type 2 inflammation at baseline, the researchers concluded dupilumab has potential for reversing airflow obstruction and may contribute to reversing airway remodeling.