Dupilumab reduces corticosteroid burdens among children with asthma

Key takeaways:

• Children on dupilumab showed lower annualized severe exacerbation rates regardless of prior exacerbation history.
• Dupilumab reduced oral corticosteroid use and improved lung function.

HONOLULU — Children with uncontrolled moderate to severe asthma experienced fewer severe exacerbations requiring systemic corticosteroids when treated with dupilumab, according to a poster presented at the CHEST Annual Meeting.

These children experienced reductions in their corticosteroid burden regardless of their prior exacerbation history, Rebecca Gall, MD, medical director, immunology, Regeneron Pharmaceuticals, and colleagues wrote.

“Despite standard-of-care therapy such as inhaled corticosteroids, children with uncontrolled moderate to severe asthma are at risk of severe asthma attacks requiring rescue courses of systemic corticosteroids (SCS),” Gall told Healio.

Rebecca Gall

The LIBERTY ASTHMA VOYAGE study and the LIBERTY ASTHMA EXCURSION extension study were designed to investigate the efficacy and safety of dupilumab (Dupixent; Regeneron/Sanofi) among children aged 6 to 11 years with uncontrolled, moderate to severe asthma in need of an additional treatment to their current maintenance management, Gall said.

“There is an opportunity to decrease SCS use in children living with moderate to severe asthma, considering its short- and long-term effects,” Gall said.

For example, Gall said, short courses of systemic immunosuppressants are effective for severe asthma attacks, but a single rescue course of SCS in children has been associated with increased risk for bleeding, sepsis and pneumonia within 30 days.

“As children get older and the lifetime total SCS dose increases, the risk of later side effects, such as heart failure, diabetes, cataracts, osteoporosis, fracture and kidney disease also increases,” Gall said.

Study design, results

The post-hoc analysis of the VOYAGE study included children aged 6 to 11 years with type 2 inflammation, defined as baseline blood eosinophil counts of 150 cells/µL or higher or fractional exhaled nitric oxide levels of 20 ppb or greater.

“Patients were stratified into two subgroups: those requiring one rescue SCS course [placebo, n = 43; dupilumab, n = 77] and those requiring two or more SCS rescue courses [placebo, n = 63; dupilumab, n = 132] in the year prior to VOYAGE,” Gall said.

These children received either 100 mg or 200 mg doses of dupilumab based on body weight or placebo every 2 weeks for 52 weeks.

Patients assigned dupilumab vs. placebo showed lower annualized severe exacerbation rates treated with rescue SCS in both the cohort with one severe prior exacerbation (0.143 vs. 0.463) and two or more severe prior exacerbations (0.477 vs. 0.839).

Additionally, the researchers found that dupilumab increased the percentage of patients without oral corticosteroid use throughout the VOYAGE and EXCURSION studies combined in both the cohort with one severe prior exacerbation (80.5% vs. 69.8%) and two or more prior exacerbations (65.9% vs. 54%).

Also, dupilumab was associated with improvements in prebronchodilator percent predicted FEV₁ regardless of number of prior severe exacerbations.

“In VOYAGE and EXCURSION, dupilumab reduced rescue SCS exposure in children with uncontrolled moderate to severe asthma as a result of reducing severe asthma attacks, regardless of the number of prior attacks,” Gall said. “Dupilumab also improved lung function.”

Conclusions, next steps

Based on these results, the researchers concluded that dupilumab led to reduced corticosteroid use related to exacerbations among children with uncontrolled moderate to severe asthma.

“These results are especially encouraging for doctors who treat children who are faced with the burden of uncontrolled moderate to severe asthma,” Gall said.

Despite treatment with current standard-of-care inhaled corticosteroids, she said, children living with moderate to severe asthma may continue to experience serious symptoms.

Also, Gall continued, these children may require the use of multiple courses of SCS that carry short- and long-term risks, and guidelines recommend careful consideration of the side effects associated with SCS.

“The LIBERTY ASTHMA VOYAGE study and its extension study LIBERTY ASTHMA EXCURSION reinforce dupilumab as an effective treatment option with an acceptable safety profile for children as young as 6 years of age living with certain types of moderate to severe asthma,” Gall said.

However, Gall advised, doctors should always refer to the approved prescribing information for dupilumab and use their own medical judgment when treating their patients.

In the meanwhile, Gall said, Regeneron and Sanofi will present additional analyses from VOYAGE and EXCURSION at future medical meetings and publish in scientific journals.

“We also continue to study dupilumab in patients with other dermatologic, respiratory and gastrointestinal conditions where type 2 inflammation may play a role,” she said.

For more information:

Rebecca Gall, MD, can be reached at rebecca.gall@regeneron.com.