Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

Abstract

BackgroundDupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers.MethodsPatients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline.ResultsDupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes.ConclusionsDupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

EAACI Biologicals Guidelines—Recommendations for severe asthma

“…Severe asthma almost always involves small airways where inhaled drugs have difficult access 216,217 . For benralizumab, dupilumab and mepolizumab, there is evidence of improving small airways obstruction 77,218,219 …”

Dupilumab for chronic eosinophilic pneumonia

“…5 It has been shown to reduce the frequency of asthma exacerbations, improve FEV1, and reduce oral steroid use in patients with severe asthma. 6 This is the first report of off-label dupilumab as a therapy to treat CEP and the first report of monoclonal antibody therapy to treat CEP in a pediatric patient. Dupilumab may be an alternative for CEP that is refractory to corticosteroids or that requires prolonged therapy.…”

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction

“…115,116 Fewer asthma attacks (~50%), 115 and reduced oral corticosteroid dependence were observed in patients receiving dupilumab when compared with placebo. 117 Dupilumab appears to be effective in patients with or without evidence of allergic asthma (raised IgE or specific IgE to aeroallergens), 118 and regardless of baseline ICS dose or lung function. However, greater benefit is observed in patients with higher baseline eosinophil and FeNO levels.…”

“…However, greater benefit is observed in patients with higher baseline eosinophil and FeNO levels. 115,118 Of 1902 patients enrolled into the phase 3 dupilumab trial, 115 107 were adolescents aged 12-17 years. In a post hoc analysis of this adolescent sub-group, significant improvements in lung function and frequency of attacks, at a similar rate seen in adults, were observed using the 200 mg dosing regimen.…”