Dupilumab improves lung function responder rates in children with asthma

Key takeaways:

• Compared with placebo, dupilumab significantly reduced severe exacerbation rates by week 12.
• Dupilumab also significantly improved pre-bronchodilator percent predicted FEV₁ over 52 weeks.

More children with asthma who were treated with dupilumab than placebo met criteria as responders in percent predicted FEV₁ measurements, according to an abstract presented at the European Respiratory Society International Congress.

These responders also experienced reduced exacerbation rates and improved lung function, Theresa W. Guilbert, MD, MS, director of the Asthma Center at Cincinnati Children’s Hospital and professor in the department of pediatrics at University of Cincinnati, said during her presentation.

“Persistent lung function impairment in children with uncontrolled moderate to severe asthma is associated with impaired quality of life and long-term risk of exacerbation and respiratory morbidity,” Guilbert said.

Theresa W. Guilbert

Dupilumab (Dupixent; Sanofi Genzyme/Regeneron) blocks the shared receptor component for IL-4 and IL-13, which Guilbert called key and central drivers of type 2 inflammation. The fully human monoclonal antibody was clinically efficacious among children aged 6 to 11 years who had uncontrolled moderate to severe type 2 asthma with a generally acceptable safety profile in the LIBERTY ASTHMA VOYAGE phase 3 study, Guilbert said.

In a post-hoc analysis of patients with type 2 asthma in the trial, the researchers evaluated lung function responder rates at week 12 — with a focus on the proportion of patients who achieved clinically meaningful improvements of at least 5% or 10% in pre-bronchodilator percent predicted FEV₁ (pre-BD ppFEV₁) — and the adjusted annualized severe exacerbation rate from week 12 to 52 among those responders.

Patients received add-on doses of 100 mg or 200 mg of dupilumab based on their body weight or a placebo every 2 weeks for 52 weeks.

At 12 weeks, a greater proportion of the treatment group than the placebo group achieved improvements in pre-BD ppFEV₁ of at least 5% (59.7%; 95% CI, 53.2%-66.1% vs. 50% 95% CI, 40.5%-59.5%) or at least 10% (44.9%; 95% CI, 38.5%-51.5% vs. 31.6%; 95% CI, 23.2%-40.9%).

Annualized severe exacerbation rates among the children who achieved 5% or greater improvements in pre-BD ppFEV₁ included 0.626 (95% CI, 0.38-1.03) among the placebo group and 0.251 (95% CI, 0.16-0.41) in the treatment group (P < .01).

Among the children who achieved 10% or greater improvements in pre-BD ppFEV₁, annualized severe exacerbation rates included 0.744 (95% CI, 0.42-1.31) for the placebo group and 0.304 (95% CI, 0.19-0.5) for the treatment group (P < .05).

“The annualized rate of severe exacerbations was reduced in dupilumab vs. placebo by 60% and 59% in patients achieving greater than or equal to 5% and greater than or equal to 10% percent predicted FEV₁ improvement at week 12, respectively,” Guilbert said.

Additionally, patients who met the ppFEV₁ responder rate criteria saw these improvements over the course of the 52-week treatment period.

“In conclusion, more patients treated with dupilumab than patients receiving placebo met the percent predicted FEV₁ responder criteria at week 12,” Guilbert said. “In these responder patients, dupilumab led to reduced exacerbation rates and improved lung function.”