Dupilumab Improves Lung Function, Reduces Asthma Flares in Patients on High-Dose ICS

Patients with type 2-high asthma who were being treated with high-dose inhaled corticosteroids (ICS) had reduced exacerbations and improved lung function when they were switched to dupilumab, according to a study published in Allergy.

ICS are a mainstay treatment of asthma, but the largest benefits are seen when they are used in low doses, with “diminishing returns” at higher doses, the authors explained. Approximately 20% of all asthma cases are considered uncontrolled, moderate-to-severe asthma and among these patients are those who have exacerbations despite their use of high-dose ICS.

“This population is at an increased risk of exacerbations, with many patients having substantially reduced lung function and impaired quality of life, all of which culminate in considerable healthcare resource use and associated cost,” they explained.

The researchers analyzed results across the dupilumab phase 2b and phase 3 LIBERTY ASTHMA QUEST studies to assess the use of the therapy on severe exacerbations, prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1), and asthma control in subgroups of patients who were taking high-dose ICS at baseline.

In the phase 2b study, 465 patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks (q2w) or every 4 weeks or placebo. The study period was 24 weeks. In the phase 3 study, 1902 patients were randomized (2:2:1:1) to receive add-on subcutaneous dupilumab 200 mg or 300 mg q2w or volume-matched placebo. The study period was 52 weeks.

At baseline for the phase 2b study, 231 patients were receiving high-dose ICS and 221 were receiving medium-dose ICS. In the phase 3 study, 929 were on high-dose and 908 were on medium-dose ICS at baseline. The authors noted that in both studies, patients receiving high-dose ICS had “worse lung function, asthma control, and prior exacerbations, indicative of their greater disease severity.”

For patients receiving high-dose ICS at baseline, dupilumab significantly reduced their adjusted annualized severe exacerbation rates. In the 2b phase, these rates were reduced by 56% on dupilumab 200 mg q2w and by 57% on dupilumab 300 mg q2w. In the phase 3 study, the rates were reduced by 46% on dupilumab 200 mg q2w and by 39% for dupilumab 300 mg q2w. For the phase 2b study, the rates were not calculated for patients receiving medium-dose ICS at baseline because “the number of events was deemed too small to provide valid estimates from an adjusted model.” In the phase 3 study, the rates were reduced by 51% on dupilumab 200 mg q2w and 53% on dupilumab 300 mg q2w.

Improved pre-BD FEV1 vs placebo was seen in patients receiving high-dose ICS at baseline dupilumab in both studies. The improvement was sustained up to 24 weeks in the phase 2b study. In the phase 3 study, the improvement was sustained over the 52-week treatment period. In both, improvements were seen bywWeek 2.

Similarly, both studies saw dupilumab improved asthma control in patients requiring high-dose ICS at baseline vs placebo. These improvements were also seen in patients when stratified by baseline eosinophils or fractional exhaled nitric oxide.

“Improvements in lung function were seen within 2 weeks, sustained throughout treatment, and generally of greater magnitude in subgroups of patients with elevated baseline levels of type 2 biomarkers,” the authors concluded.

Reference

Bourdin A, Papi AA, Corren J, et al. Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline. Allergy. Published online October 3, 2020. doi: 10.1111/all.14611