Dupilumab Improved Lung Function, Reduced Asthma Exacerbations

William W. Busse, MD

A post hoc analysis of data from the phase 3 LIBERTY ASTHMA QUEST study found that dupilumab (Dupixent) significantly reduced severe asthma exacerbations and improved lung function in patients with moderate-to-severe asthma, both with and without comorbid allergic rhinitis (AR).

“Dupilumab significantly improved FEV₁ and reduced annual severe exacerbation rates in this difficult-to-control asthma population with comorbid AR and also in patients without concomitant AR,” wrote investigator William W. Busse, MD, University of Wisconsin School of Medicine and Public Health, Madison, WI, and colleagues in their abstract, which was presented at the 2019 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Francisco, CA.

The LIBERTY ASTHMA QUEST study included 1902 participants, of whom 1207 (63.5%) had self-reported comorbid allergic rhinitis and 695 did not. Participants were randomized (2:2:1:1) to dupilumab 300 mg with a 600 mg loading dose (n = 633), dupilumab 200 mg with 400 mg loading dose (n = 631), placebo 2 mL to match the dupilumab 300 mg group (n = 321), and placebo 1.14 mL to match dupilumab 200 mg group (n = 317). All groups received treatment subcutaneously every 2 weeks over a treatment period of 52 weeks.

Dupilumab significantly reduced annual severe asthma exacerbations during the 52-week treatment period in patients with comorbid AR and without comorbid AR. For patients with comorbid AR, dupilumab 200 mg reduced the adjusted annualized severe exacerbation rate by 39%, for dupilumab 300 mg, that reduction was 41% (P <.001 versus placebo for both).

For patients without comorbid AR, dupilumab 200 mg reduced the exacerbation rate by 59% and dupilumab 300 mg reduced that rate by 54% (P <.001 versus placebo for both).

The study also evaluated the effect of dupilumab on pre-bronchodilator FEV₁. Patients with comorbid allergic rhinitis receiving dupilumab 200 mg and 300 mg experienced improved pre-bronchodilator FEV₁ from baseline to week 12 by LS mean 0.14 L and 0.17 L, respectively (both P <.0001).

In patients without AR, dupilumab 200 mg significantly improved pre-bronchodilator FEV₁ at week 12 by LS mean 0.13 L compared to placebo (P = .003). However, by week 6, the placebo effect was stronger for those receiving placebo 2 mL than those receiving 1.14 mL. Therefore, the improvement in FEV₁ seen in the dupilumab 300 mg group versus placebo 2 mL was not significant past week 6.

“Improvements in pre-bronchodilator FEV₁ were observed as early as Week 2 and were sustained throughout the 52-week treatment period in all subgroups with the exception of patients without comorbid AR receiving dupilumab 300 mg q2w,” wrote the investigators.

Overall, treatment emergent adverse events (TEAEs) occurred in 81% versus 83% for dupilumab-treated and placebo-treated patients, respectively. The most common TEAEs were viral upper respiratory tract infection (dupilumab, 18% versus placebo, 20%), injection-site erythema (14% versus 6%), upper respiratory tract infection (12% versus 14%), and bronchitis (11% versus 14%).

The abstract, “Dupilumab Improves Lung Function and Reduces Severe Exacerbation Rate in Patients With Uncontrolled, Moderate-to-Severe Asthma With or Without Comorbid Allergic Rhinitis: Results From the Phase 3 LIBERTY ASTHMA QUEST Study,” was presented as a poster at the Annual Meeting of AAAAI on Sunday, February 23, 2019.