Analyses from 2 trials confirm biologic’s benefit

Based largely on findings from the Liberty Asthma trials, the FDA approved the biologic drug dupilumab (Dupixent) to treat children 6 to 11 years of age with eosinophilic phenotype or oral corticosteroid-dependent asthma—and now, CHEST 2021 has provided a deeper dive into those trials with analyses of the initial findings from the pivotal Liberty Asthma Voyage trial and new data from the Liberty Asthma Venture trial. Those paired presentations confirmed that among young children with certain types of uncontrolled asthma, treatment with dupilumab improved lung function.

Compared to placebo, dupilumab treatment was associated with significantly improved predicted pre- and post-bronchodilator FEV1 in the Liberty Asthma Voyage study, which enrolled children between the ages of 6 and 11 with uncontrolled asthma and either blood eosinophils ≥150 cells/μl (eosinophilic phenotype) or fractional exhaled nitric oxide (FENO) ≥20 ppb at baseline, Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, and colleagues explained in their poster presentation. However, still unknown were “the effects on additional lung function parameters,” they wrote.

The trial randomized a total of 408 children (2:1) to receive add-on dupilumab 200 mg or 100 mg every two weeks based on body weight (>30 kg or ≤30 kg), or matched placebo every two weeks for 52 weeks. Of the total cohort enrolled in Voyage, 350 met the type 2 phenotype criteria, including 236 who were treated with dupilumab and 114 treated with placebo. Absolute and percent predicted changes in pre-bronchodilator FEV1, post-bronchodilator FEV1, pre-bronchodilator forced expiratory flow 25–75% (FEF25–75%), and forced vital capacity (FVC) from baseline during the treatment period were analyzed in patients with a T2 inflammatory asthma phenotype.

“Pre-bronchodilator FEV1 (L) improved from baseline in dupilumab- versus placebo-treated patients with a least squares (LS) mean difference at week 2 of 0.06L (95% CI, 0.01–0.12; P=0.025); and at week 52 of 0.17L (95% CI, 0.09–0.24; P<0.0001),” Bacharier et al reported. Similar benefits were seen in post-bronchodilator FEV1, with an LS mean difference versus placebo of 0.09L (95% CI, 0.02–0.16, P=0.015) at week 52.

Dupilumab also improved post-bronchodilator FEV1pp: 89.66 (placebo) versus 93.36 (dupilumab) by week 52 (LS mean difference: 4.37 percentage points (95% CI, 0.95–7.78); P=0.012).

Researcher Christian Domingo Ribas, MD, FCCP, of Autonomous University of Barcelona, Barcelona, Spain, and colleagues presented a post hoc analysis of the companion Liberty Asthma Venture trial. They noted that a small number of asthma patients—somewhere between 5% and 10%—develop severe disease, and more than a third of these patients require daily oral corticosteroids. In their poster, Ribas and colleagues investigated whether treatment with dupilumab could reduce corticosteroid use and improve clinical outcomes, regardless of baseline oral corticosteroid use, in patients age 12 years and older with uncontrolled asthma.

“Treatment with dupilumab was found to reduce daily oral corticosteroid dose from baseline at week 24 in patients with baseline oral corticosteroid doses of <10 mg/day and ≥10 mg/day,” Ribas et al reported.

Among patients in the lower baseline oral corticosteroid group, 72% of dupilumab-treated patients and 42% of placebo-treated patients no longer required oral corticosteroids at week 24 (odds ratio, 3.8; 95% CI, 1.4–10.0; P<0.01). Among patients in the higher baseline oral corticosteroid group, 37% of dupilumab- and 23% of placebo-treated patients were no longer using oral corticosteroids at week 24 (OR, 2.3; 95% CI, 1.0–5.4; P<0.05).

Treatment with dupilumab was also associated with 71% and 48% reductions in the annualized rate of severe asthma exacerbations among patients in the lower baseline and higher baseline oral corticosteroid groups, respectively.

Ribas and colleagues concluded that, “in patients with oral corticosteroid-dependent, severe asthma, dupilumab significantly reduced oral corticosteroid dose and improved the likelihood of no longer requiring oral corticosteroids at week 24, irrespective of baseline dose.”

  1. Be aware that among children age 6 to 11 with certain types of uncontrolled asthma, treatment with dupilumab improved lung function.

  2. Treatment with dupilumab was associated with a reduction in oral corticosteroid use and improved clinical outcomes regardless of baseline oral corticosteroid use in patients age 12 years and older.

Salynn Boyles, Contributing Writer, BreakingMED™

The Liberty Asthma Voyage and Liberty Asthma Venture trials were funded by Sanofi and Regeneron.

Researcher Leonard B. Bacharier reported receiving speakers fees from AstraZeneca, GSK, Regeneron Pharmaceuticals, Inc., Sanofi; serving on safety monitoring boards for Cystic Fibrosis Foundation, DBV Technologies; receiving research support from the NIH, Sanofi, Vectura. Teresa Guilbert reported receiving personal fees from the American Board of Pediatrics, AstraZeneca, GSK, Novartis, Pediatric Pulmonary Subboard, Regeneron Pharmaceuticals, Inc., Sanofi, Teva; grants from AstraZeneca, NIH, Regeneron Pharmaceuticals, Inc., Sanofi; and royalties fromUpToDate.

Researcher Christian Domingo Ribas reported receiving travel and speaker fees from ALK, Allergy Therapeutics, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer Pharma, GSK, HAL Allergy, ImmunoTek, Menarini, Novartis, Pfizer, sanofi-aventis, Stallergenes Greer, Takeda, Teva.

Cat ID: 195

Topic ID: 89,195,730,100,138,637,192,195,225,63,925,224