Dupilumab may reduce exacerbations in paediatric uncontrolled asthma
Children with uncontrolled moderate-to-severe asthma may benefit from treatment with dupilumab which reduced exacerbations and improved lung function, according to results of the phase III VOYAGE study presented at ATS 2021.
“Dupilumab demonstrated efficacy and an acceptable safety profile in patients aged 6 to <12 years with uncontrolled, moderate-to-severe asthma with a type 2 inflammatory phenotype,” noted the study authors.
Participants were 408 children aged 6 to <12 years with moderate-to-severe asthma whose condition was uncontrolled despite high-dose inhaled corticosteroids (ICS) alone or medium-to-high-dose ICS with a second asthma controller. Of these, 350 children had type 2 inflammatory asthma phenotype, defined by baseline blood eosinophil levels of ≥150 cells/μL or fractional exhaled nitric oxide (FeNO) ≥20 ppb, and 259 had baseline blood eosinophil levels of ≥300 cells/μL. They were randomized 2:1 in a double-blind fashion to receive subcutaneous dupilumab (100 or 200 mg Q2W for those weighing ≤30 or >30 kg, respectively) or placebo for 52 weeks.
At week 12, among patients with type 2 phenotype, annualized rate of severe asthma exacerbations was reduced by 59.3 percent in the dupilumab vs placebo group (relative risk [RR], 0.407, 95 percent confidence interval [CI], 0.274–0.605; p<0.0001). [ATS 2021, abstract A1204]
Similarly, dupilumab led to a significant 64.7 percent reduction in annualized exacerbation rate vs placebo among patients with baseline blood eosinophils ≥300 cells/μL (RR, 0.353, 95 percent CI, 0.222–0.562; p<0.0001).
There was also a significant improvement from baseline in pre-bronchodilator FEV1 percent predicted (FEV1 pp) with dupilumab vs placebo at week 12 in both the type 2 phenotype (least squares [LS] mean change, 5.32 vs 10.53; LS mean difference, 5.21; p=0.0009) and baseline blood eosinophils ≥300 cells/μL (LS mean change, 4.83 vs 10.15; LS mean difference, 5.32; p=0.0036) populations.
There were also smaller reductions from baseline in FeNO levels with dupilumab vs placebo at week 12 in the type 2 phenotype (LS mean change, -1.13 vs -18.97; LS mean difference, -17.84 ppb) and baseline blood eosinophils ≥300 cells/μL (LS mean change, -0.81 vs -21.40; LS mean difference, -20.59 ppb) populations (p<0.0001 for both).
At week 24, there was a greater improvement in Asthma Control Questionnaire-Interviewer Administered (ACQ-7-IA) scores with dupilumab vs placebo (LS mean difference, -0.33 and -0.46 in the type 2 phenotype and baseline blood eosinophils ≥300 cells/μL populations, respectively; p<0.0001 for both).
Treatment-emergent adverse event (TEAE) rates were comparable between the dupilumab and placebo arms (83 percent vs 80 percent), as were serious TEAEs (4.8 percent vs 4.5 percent). Permanent study discontinuation due to AEs occurred in 1.8 and 1.5 percent of dupilumab and placebo recipients, respectively.
By week 52, median blood eosinophils had decreased to below baseline levels in the dupilumab group.
“The effect of dupilumab on improving lung function in these children was particularly impressive,” said study author Professor Leonard Bacharier from the Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tennessee, US.
“Decreased lung function is associated with an increased risk of future asthma exacerbations. In addition, impaired lung function can result in abnormal lung growth. In this trial, dupilumab demonstrated significant and rapid improvement in lung function within 2 weeks that was sustained for up to 52 weeks, compared to placebo,” he added.
“We hope results from the VOYAGE trial will lay the groundwork for dupilumab as a potential new treatment option for patients aged 6 to 11 with moderate-to-severe asthma. We also hope this study will lead to better characterization and understanding of the role of type 2 inflammation in asthma in paediatric patients,” Bacharier concluded.