NEW ORLEANS — Patients diagnosed with asthma at age 40 and beyond showed better responses to the interleukin-4 receptor agonist dupilumab (Dupixent) than patients with earlier-onset asthma, according to a subanalysis of the LIBERTY ASTHMA QUEST study reported here.
And in a separate analysis of data from the companion LIBERTY ASTHMA VENTURE trial, which enrolled patients with corticosteroid-dependent severe asthma, treatment with dupilumab was associated with exacerbation reductions in patients with and without early measurable improvements in lung function.
Nicola Hanania, MD, of Baylor College of Medicine in Houston, presented the post hoc analysis from the two trials at CHEST 2019, sponsored by the American College of Chest Physicians.
In the year-long LIBERTY ASTHMA QUEST trial, initially reported in June 2018, patients with uncontrolled, moderate-to-severe asthma treated every 2 weeks with injections of dupilumab showed a roughly 48% reduction in exacerbations, compared with patients given placebo injections.
Hanania explained that the rationale for the post hoc analysis is that age of asthma onset is an important variable in disease course, presence of comorbidities, and response to therapy.
Late-onset asthma was defined as asthma presenting at age 40 or older. At baseline, patients with late-onset asthma had lower mean pre-bronchodilator forced expiratory volume in 1 second (FEV1) than patients with early-onset disease (1.52 vs 1.88 mL), and fewer late-onset patients had ongoing atopic conditions (71.1% vs 86.6%).
The mean number of exacerbations in the previous year and mean level of blood eosinophil counts were similar in the two groups, as was baseline fractional exhaled nitric oxide (FeNO).
The analysis showed that dupilumab at 200 mg and 300 mg once every 2 weeks vs placebo significantly reduced severe exacerbations by 38.1% (P=0.0009) and 37.3% (P=0.0007), respectively, in patients with early-onset asthma and by 63.7% and 68.5%, respectively, in patients with late-onset disease (both P<0.0001).
Dupilumab use was also associated with significant improvements in FEV1 in both the early- and late-onset groups, and the biologic therapy was generally well-tolerated in both groups.
“The magnitude of effect observed for FEV1 was numerically similar in both groups,” Hanania said. “Greater treatment effects were observed in patients with elevated blood eosinophils or FeNO in both groups.”
The post hoc analysis from the ASTHMA VENTURE trial (also with main findings reported in June 2018) stratified patients by “clinically meaningful improvements” of 100 mL or more or 200 mL or more in pre-bronchodilator FEV1 at week 12.
The original findings from the trial showed that treatment with dupilumab reduced exacerbations and oral glucocorticoid dependence in patients with glucocorticoid-dependent severe asthma.
By week 12 of the study, significantly more patients treated with dupilumab saw improvements in pre-bronchodilator FEV1 of 100 mL or more (65.7% vs 33%; P<0.0001) or 200 mL or more (49.5% vs 23.8%, P=0.0002), compared with patients in the placebo arm.
This improvement was associated with significantly fewer severe exacerbations during the 24-week period (72% lower and 71.9% lower, respectively, P=0.0003).
Patients who had less than a 100 mL reduction in pre-bronchodilator FEV1 had a 45% reduction in exacerbations, compared with similar patients in the placebo arm of the trial, while those with less than a 200 mL reduction had a 67% reduction, compared with placebo-treated patients.
The most frequent treatment-emergent adverse event in the dupilumab-treated patients was transient eosinophilia (14% vs 1%).
“In this post hoc analysis, dupilumab reduced severe asthma exacerbations in the 24-week treatment period in oral corticosteroid-dependent patients with and without clinically meaningful improvements in lung function at week 12,” Hanania said.
The Asthma QUEST and Asthma VENTURE trials were funded by Sanofi and Regeneron Pharmaceuticals.
Hanania reported financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron, and Sanofi.
Lead investigator Mario Castro reported receiving grants from Sanofi and Regeneron Pharmaceuticals and non-financial support from Excerpta and Medica BV during the conduct of the studies.
last updated 10.24.2019