Patients with moderate-to-severe asthma who received dupilumab every 2 weeks had reduced acute severe exacerbations and improved lung function regardless of their bronchodilator reversibility status, according to recent research from a post-hoc analysis scheduled for presentation at the American Thoracic Society in Dallas.

“Dupilumab reduced severe exacerbations and improved lung function in uncontrolled moderate-to-severe asthma patients with low and high baseline post-bronchodilator [forced expiratory volume in 1 second] FEV₁ reversibility and was generally well tolerated,” Ian Pavord, FMedSci, FRCP, from the University of Oxford in Oxford, United Kingdom, and colleagues wrote in their study abstract.

Convention center. Source: Getty

Dupilumab is a human monoclonal antibody that targets anti-interleukin (IL)-4 receptor α and inhibits IL-4/IL-13, which drives type 2 inflammation. In the United States, dupilumab has been approved for use in adolescents with moderate-to-severe eosinophilic or corticosteroid-dependent asthma in cases where asthma is inadequately controlled by topical therapies. The phase 3 Liberty Asthma QUEST trial found patients who received dupilumab as an add-on therapy at a dose of 200 mg or 300 mg every 2 weeks had “significantly reduced severe exacerbations, improved pre-bronchodilator forced expiratory volume in 1 second (FEV₁), and improved quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma.” Patients with elevated type 2 inflammation biomarkers, such as blood eosinophils at ≥ 150cells/µL or fractional exhaled nitric oxide (FeNO) at ≥ 25ppb, saw greater treatment effects, the researchers said.

In a post-hoc analysis, Pavord and colleagues evaluated the effects of dupilumab among patients with high and low bronchodilator reversibility, which was defined as “above or below the overall population median (20.89%).”

Patients inhaled a beta2-agonist between 2 times and 4 times at baseline and had ≥ 12% bronchodilator reversibility and 200 mL in FEV₁. The researchers examined the rate of severe exacerbations per year and the change in FEV₁ before and after bronchodilator and change in forced expiratory flow at 25% to 75% of pulmonary volume (FEF25-75%) before bronchodilator use when compared with baseline.

There was a reduced number of severe exacerbations among patients taking dupilumab with low bronchodilator reversibility groups in 200 mg doses (─41.9%; P = .002) and 300 mg doses (─58.5%; P < .0001), and in high bronchodilator reversibility groups in 200 mg doses (─52.6%; P < .0001) and 300 mg doses (─26.8%; P = .06). Patients with low bronchodilator reversibility had higher FEV1 and FEF25-75% scores than patients with high bronchodilator reversibility.

Compared with the placebo group, patients receiving dupilumab had improved least square mean change in FEV₁ before and after bronchodilator at 12 weeks and 52 weeks in low and bronchodilator reversibility groups (LS mean difference vs placebo range, 0.07─0.28L and 0.07─0.27L). With regard to FEF25-75% at 12 weeks and 52 weeks, there was a significant improvement in LS mean change before and after bronchodilator use compared with the placebo group (LS mean difference vs placebo range 0.10─0.25L/s) with a non-significant improvement at 12 weeks for patients with high bronchodilator reversibility.