NEW ORLEANS – A new analysis suggests
Dr. Nicola Hanania
Dupilumab may be more effective in reducing severe asthma exacerbations in patients with late-onset asthma, but the drug’s effect on lung function appeared the same regardless of asthma onset. Nicola Hanania, MD, of Baylor College of Medicine in Houston presented these results at the annual meeting of the American College of Chest Physicians.
Dr. Hanania and colleagues conducted a subanalysis of the LIBERTY ASTHMA QUEST study (NCT02414854). Previous data from this study showed that patients with uncontrolled, moderate to severe asthma who received dupilumab had fewer exacerbations and better lung function than did patients who received placebo (N Engl J Med. 2018;378:2486-96).
In their subanalysis, Dr. Hanania and his colleagues evaluated the efficacy of dupilumab, given at 200 mg or 300 mg every 2 weeks, in patients with early-onset asthma (at 40 years of age or younger) and late-onset asthma (at 41 years or older). The analysis included 919 patients with early-onset asthma who received dupilumab and 450 early-onset patients who received placebo. There were 345 patients with late-onset asthma who received dupilumab and 188 late-onset patients who received placebo.
Exacerbations
Dupilumab significantly reduced the adjusted annualized severe exacerbation rates during the 52-week treatment period. Significant reductions occurred in both early- and late-onset patients, though reductions were greater in the late-onset group.
In early-onset patients, dupilumab reduced severe exacerbations by 38% when given at 200 mg and by 37% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients, dupilumab reduced exacerbations by 64% and 69%, respectively (P less than .001 vs. placebo).
Dr. Hanania said it isn’t clear why late-onset patients appear to derive more benefit with regard to exacerbations. It may be because these patients have more comorbidities or because they aren’t using their inhalers correctly. The researchers are investigating these possibilities.
Dr. Hanania went on to note that reductions in exacerbation rates were greatest in patients with elevated blood eosinophils (150 cells/mcL or greater) or fractional exhaled nitric oxide (FeNO; 25 ppb or greater).
In patients with early-onset asthma and elevated eosinophils, dupilumab reduced severe exacerbations by 50% when given at 200 mg and by 55% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated eosinophils, dupilumab reduced exacerbations by 65% and 73%, respectively (P less than .001 vs. placebo).
In patients with early-onset asthma and elevated FeNO, dupilumab reduced severe exacerbations by 56% when given at 200 mg and by 52% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated FeNO, dupilumab reduced exacerbations by 79% and 71%, respectively (P less than .001 vs. placebo).
Lung function
Dupilumab also improved prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1), compared with placebo, with similar results in early- and late-onset patients.
In early-onset patients, the P values were less than .001 for both doses of dupilumab at weeks 12 and 52. In late-onset patients, the P values were less than .001 for the 300-mg dose at week 12 and the 200-mg dose at week 52, less than .01 for the 200-mg dose at week 12, and less than .05 for the 300-mg dose at week 52.
The effects of dupilumab on pre-BD FEV1 were greatest in patients with elevated eosinophils or FeNO. At week 12, the P value was less than .001 for both doses of dupilumab in early-onset patients with elevated eosinophils or FeNO. The P value was less than .01 for both doses in late-onset patients with elevated eosinophils. And the P value was less than .001 for both doses in late-onset patients with elevated FeNO.
This research was sponsored by Sanofi and Regeneron. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.870.