Children with asthma have fewer exacerbations with dupilumab despite disease duration

Key takeaways:

• Children with uncontrolled, moderate to severe asthma used dupilumab or placebo for 52 weeks.
• The treatment group had significant decreases in annualized exacerbation rates compared with the placebo group.

SAN FRANCISCO — Children with asthma experienced fewer exacerbations and better control with dupilumab regardless of the duration of their disease, according to a poster at the American Thoracic Society International Conference.

But children with longer durations of asthma had more exacerbations and less control, Wanda Phipatanakul, MD, MS, director, division of immunology research center, Boston Children’s Hospital, said during her presentation.

“There is evidence that increased length of time with asthma can increase symptoms and lead to persistent disease,” Phipatanakul told Healio. “We wanted to understand whether disease duration affected how dupilumab impacted key clinical outcomes.”

Wanda Phipatanakul

The 52-week, double-blind, phase 3 VOYAGE trial included 350 children aged 6 to 11 years with uncontrolled, moderate to severe type 2 inflammatory asthma, defined as blood eosinophil counts of 150 cells/µL or higher or fractional exhaled nitric oxide of 20 parts per billion or higher.

“The average patient age was 9 years, and 64% were male. Approximately 5% of patients were Black/African American, 0.5% were Asian/Asian American and 0.2% were American Indian/Alaska Native,” Phipatanakul said. “This population reflected the demographic makeup of the study regions.”

Children received dupilumab (Dupixent; Sanofi, Regeneron) in 100 mg or 200 mg doses depending on body weight or placebo every 2 weeks in a 2:1 randomized ratio.

Cohorts included children who had asthma for 4 years or fewer (37.7% of placebo group and 31.8% of dupilumab group), more than 4 to fewer than 7 years (36.8% of placebo group and 36.9% of dupilumab group) or 7 years or more (25.4% of placebo group and 31.4% of dupilumab group).

Percentages of children who did not experience any severe exacerbations included 72.1% of those on placebo and 86.7% of those on dupilumab among those with asthma for 4 years or less (P = .0439); 54.8% of those on placebo and 71.3% of those on dupilumab among those with asthma for more than 4 to fewer than 7 years (P = .0359); and 48.3% of those on placebo and 74.3% of those on dupilumab among those with asthma for 7 years or longer (P = .0046).

Compared with the placebo group, the dupilumab group also experienced significant decreases in adjusted annualized exacerbation rates and improvements in control, defined as scores of 0.75 and lower on the Interviewer-Administered 7-item Asthma Control Questionnaire.

Percentages of children who reported well-controlled asthma included 55.8% of those on placebo and 78.7% of those on dupilumab among those with asthma for 4 years or less (P = .011); 42.9% of those on placebo and 67.8% of those on dupilumab (P = .0104) among those with asthma for more than 4 to fewer than 7 years; and 34.5% of those on placebo and 62.2% of those on dupilumab with asthma for 7 years or longer (P = .0189).

Phipatanakul called the percentages of exacerbation reductions with dupilumab compared with placebo in patients with asthma for 4 years or less and patients with asthma for 7 years or longer older very similar.

“Though a higher proportion of patients with shorter disease durations experienced disease control and absence of severe exacerbations overall, the majority of patients in each dupilumab group experienced these outcomes regardless of how long they’d had the disease and were significantly more likely than those on placebo to experience them,” she said.

Based on these findings, the researchers concluded that dupilumab decreased annualized exacerbation rates and improved control among children with uncontrolled moderate to severe type 2 asthma.

“The fact that dupilumab improves outcomes regardless of previous asthma duration further emphasizes its already well-established safety and efficacy,” Phipatanakul said.

“This is especially important for young children who are particularly vulnerable as their lungs are still developing, so reducing exacerbations and improving control could help reduce the impact of persistent symptoms on the lungs,” she continued.

Phipatanakul noted that there are no restrictions on the duration of asthma before dupilumab can be prescribed.
“But these data show physicians that regardless of the duration of their patient’s disease, dupilumab can provide clinically meaningful improvements in signs and symptoms in children,” she said.

For more information:

Wanda Phipatanakul, MD, MS, can be reached at wanda.phipatanakul@childrens.harvard.edu.