Dupilumab Efficacy in Patients Stratified by Baseline Treatment Intensity and Lung Function.
Pavord ID., Siddiqui S., Papi A., Corren J., Sher LD., Bardin P., Langton D., Park H-S., Rice MS., Deniz Y., Rowe P., Staudinger HW., Patel N., Ruddy M., Graham NMH., Teper A.
<h4>Purpose</h4>The Phase 3 LIBERTY ASTHMA QUEST study in patients aged ≥12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks (q2w) vs matched placebo in the overall population. This post hoc analysis assessed dupilumab efficacy by disease severity as evidenced by baseline % predicted forced expiratory volume in 1 second (FEV<sub>1</sub>) and dose of inhaled corticosteroids (ICS).<h4>Patients and methods</h4>Severe asthma exacerbation rates, change from baseline in FEV<sub>1</sub>, asthma control, quality of life, and fractional exhaled nitric oxide (FeNO) levels over the 52-week treatment period were assessed in patients with elevated type 2 inflammation biomarkers stratified by ICS dose and FEV<sub>1</sub>% predicted at baseline.<h4>Results</h4>In patients with elevated baseline eosinophils, dupilumab 200 mg and 300 mg q2w vs placebo reduced severe exacerbation rates by 50% (<i>P</i>=0.06) and 67% (<i>P</i>=0.001), respectively, in those with medium-dose ICS/FEV<sub>1</sub>% predicted 60-90%, and by 59% (<i>P</i><0.001) and 47% (<i>P</i>=0.006) in those with high-dose ICS/FEV<sub>1</sub>% predicted <60%, improved pre-bronchodilator FEV<sub>1</sub> at Week 12 by 0.16L (<i>P</i>=0.005) and 0.08L (<i>P</i>=0.13), and by 0.20L (<i>P</i>=0.003) and 0.21L (<i>P</i><0.001), respectively, in the same subgroups. Dupilumab vs placebo also improved asthma control and quality of life and suppressed FeNO levels in all patient subgroups with similar results observed irrespective of baseline biomarker status or disease severity.<h4>Conclusion</h4>Dupilumab reduced severe exacerbations and improved lung function, asthma control and quality of life in patients with elevated baseline eosinophils irrespective of baseline ICS dose or FEV<sub>1</sub>% predicted.