Uncontrolled Asthma: Dupilumab Shows Efficacy Regardless of Disease Severity

Takeaway

• In patients with uncontrolled, moderate-to-severe asthma and elevated baseline eosinophils, dupilumab reduced severe exacerbations and improved lung function, asthma control and quality of life (QoL), regardless of their baseline disease severity defined by baseline inhaled corticosteroids (ICS) requirement or percentage predicted forced expiratory volume in 1 second (FEV₁%).

Why this matters

• Findings suggest that dupilumab should be considered as an add-on maintenance treatment for uncontrolled, moderate-to-severe asthma in patients with elevated blood eosinophils or fractional exhaled nitric oxide (FeNO), on medium-dose ICS and FEV1% predicted ≥60-90%, and those on high-dose ICS and FEV1% predicted <60%.

Study design

• In phase 3 LIBERTY ASTHMA QUEST study, 1902 patients aged ≥12 years with uncontrolled, moderate-to-severe asthma were randomly assigned in a 2:2:1:1 ratio to add-on subcutaneously administered dupilumab 200 mg or 300 mg every 2 weeks (q2w) or matched-volume placebo for 52 weeks.
• In this post hoc analysis, severe exacerbation rates, change in pre-bronchodilator FEV1, asthma control, QoL and FeNO levels were assessed in patients with elevated type 2 inflammation biomarkers stratified by baseline ICS dose and FEV1% predicted.
• Funding: Sanofi and Regeneron Pharmaceuticals, Inc.

Key results

• In patients with elevated baseline eosinophils, dupilumab 200 mg and 300 mg (q2w) vs placebo reduced severe exacerbation rates by:
  • 50% (P=.06) and 67% (P=.001), respectively, in patients (n=517) on medium-dose ICS with high FEV₁% predicted; and
  • 59% (P<.001) and 47% (P<.01), respectively, in those (n=520) on high-dose ICS with low FEV₁% predicted.
• At 12 weeks, dupilumab 200 mg and 300 mg (q2w) vs placebo improved pre-bronchodilator FEV₁ by 0.16 L (P=.005) and 0.08 L (P=.131) and by 0.20 L (P=.003) and 0.21 L (P<.001), respectively, in the same subgroups.
• Similarly, dupilumab 200 mg and 300 mg (q2w) vs placebo improved asthma control (as measured by 5-item Asthma Control Questionnaire score) and QoL (as measured by Asthma Quality of Life Questionnaire score) and suppressed FeNO levels in all patient subgroups, irrespective of baseline biomarker status or disease severity.

Limitations

• Post hoc analysis.

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.