麻豆传媒

SEATTLE -- Add-on treatment with the biologic therapy dupilumab (Dupixent) was associated with reduced severe exacerbations and improved lung function in patients with allergic asthma in a post-hoc analysis of phase III data from the study reported here.

The analysis compared outcomes in patients with allergic disease versus those without, with endpoints of exacerbation rates and the FEV1 measure of lung function. Allergic asthma was defined as total serum immunoglobulin (Ig)E ≥30 kU/L and ≥1 positive perennial aeroallergen-specific IgE (≥0.35 kU/L) at baseline.

As by Mario Castro, MD, of Washington University in St. Louis, at the American College of Allergy, Asthma & Immunology annual scientific meeting, a total of 56% of the intent-to-treat population (n=1,066) met the criteria for allergic asthma. In patients with and without allergic asthma, dupilumab versus placebo significantly reduced annualized severe exacerbation rates during the treatment period. In both subgroups, improvements were greater with higher baseline blood eosinophil and fractional exhaled nitric oxide levels.

Among the specific findings:

• Change from baseline FEV₁ to week 12 in patients who met criteria for allergic asthma treated with 200 mg dupilumab every 2 weeks versus placebo was least square mean 0.31 ± 0.02 versus 0.18 ± 0.03 (P<0.001)
• Change from baseline FEV₁ to week 12 in patients who met allergic asthma criteria treated with 300 mg dupilumab every 2 weeks versus placebo was 0.35 ± 0.02 versus 0.19 ± 0.03 (P<0.001)
• Dupilumab reduced total IgE in patients with and without allergic asthma, and side effects were usually well tolerated

The most frequent adverse event in the dupilumab-treated groups versus placebo was injection-site reactions (15%/18% versus 5%/10%, respectively).

"For the post-hoc analysis we compared outcomes in patients with and without evidence of allergic disease and found that the response rate in terms of exacerbations and lung function increases were similar in the two populations," Castro told 麻豆传媒.

The researchers concluded that add-on dupilumab reduced severe exacerbations and improved lung function in patients with allergic and non-allergic uncontrolled, moderate-to-severe asthma and was generally well tolerated.

"Clinically, it is important to look at whether this drug works in patients with allergic disease," Castro told 麻豆传媒. "We have other treatments for these patients, such as anti-IgE therapies, but the more options we have the better."

Original findings from the Sanofi and Regeneron Pharmaceuticals-sponsored trial, published in the , showed dupilumab treatment to be associated with significantly lower rates of severe asthma exacerbation compared with placebo, as well as better lung function and asthma control in patients with moderate-to-severe uncontrolled asthma. Greater benefits were seen in patients with higher baseline levels of eosinophils.

Dupilumab is a fully human interleukin (IL)-4 receptor-α monoclonal antibody inhibiting IL-4/IL-13 signaling pathways, which are key drivers of Type 2 inflammation.

Originally approved by the FDA in March 2017 as an add-on treatment for atopic dermatitis, the biologic therapy was approved for an asthma indication last month, as an add-on maintenance therapy for patients ages 12 and older with either eosinophilic or oral corticosteroid-dependent asthma.

In the phase III Liberty Asthma Quest study, dupilumab administered at 200 and 300 mg every 2 weeks versus matched placebo was shown to reduce annualized severe exacerbation rates and improve pre-bronchodilator lung function, as measured by FEV₁, as well as improve quality-of-life measures, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma.