IL-4/13 blocker successful in treatment of paediatric moderate-to-severe asthma

Dupilumab reduced annualised exacerbations in schoolchildren with uncontrolled moderate-to-severe asthma by >50% compared with placebo. The safety profile was similar to that seen in adolescents and adults. These were the results of the VOYAGE trial.

Despite optimised standard-of-care therapy, children with moderate-to-severe asthma may continue to have uncontrolled disease. The IL-4/13 blocker dupilumab has previously been shown to be effective and has a demonstrated favourable safety profile in adolescents and adults with moderate-to-severe asthma [1]. Prof. Leonhard B. Bacharier (Vanderbilt University Medical Center, TN, USA) presented results of the VOYAGE trial (NCT02948959) and pointed out that type 2 inflammation underlies most cases of asthma in children [2]. The VOYAGE trial aimed to assess the efficacy of dupilumab in children aged 6–11 with uncontrolled moderate-to-severe asthma. Enrolled in the trial were 408 children. Patients receiving high-dose inhaled corticosteroids (ICS) alone or a medium-to-high dose ICS with a second asthma controller were randomised 2:1 to receive 100 mg (body weight ≤30 kg) or 200 mg (>30 kg) subcutaneous dupilumab or a matched placebo for up to 52 weeks.

The researchers performed pre-specified primary analyses in 2 populations in the study: 350 patients with markers of type 2 inflammation (baseline blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide (FeNO) ≥20 ppb) and 259 patients with baseline blood eosinophils ≥300 cells/μL.

At the end of the trial, dupilumab significantly reduced the annualised rate of severe exacerbations versus placebo by 59.3% in the type 2 inflammation phenotype and by 65% in the population with baseline blood eosinophils ≥300 cells/μL (P<0.0001 for both comparisons; see Figure). In addition, the treatment improved the pre-bronchodilator forced expiratory volume in the first second (FEV₁) percent of predicted at week 12, a key secondary endpoint, in both populations and reduced FeNO significantly at 12 weeks compared with placebo. The biologic led to rapid and sustained lung function improvement over the entire treatment period in both populations. At week 24, patients treated with dupilumab showed greater improvement in asthma control scores as compared with the placebo group.

Figure: Dupilumab significantly reduced the annualised rate of severe exacerbations versus placebo [2]



eos, eosinophils; FeNO, fractional exhaled nitric oxide; ITT, intention-to-treat.

The safety profile of dupilumab was generally consistent with the known safety profile of dupilumab in patients aged ≥12 years with moderate-to-severe asthma. “There were 7 parasitic infections, 5 of those were enterobiasis, but they were not serious and did not lead to treatment discontinuation,” Prof. Bacharier explained.

“The effect of dupilumab on improving lung function in these children was particularly impressive,” noted Dr Bacharier. “Decreased lung function is associated with an increased risk of future asthma exacerbations. In addition, impaired lung function may result in abnormal lung growth,” he concluded.

1. Castro M, Corren J, Pavord ID, et al. N Engl J Med 2018;378(26):2486-96.
2. Bacharier LB, et al. Dupilumab efficacy and safety in children with uncontrolled, moderate-to-severe asthma: The phase 3 VOYAGE study. Session B007: Breaking news: clinical trial results in pulmonary medicine. ATS 2021 International conference, 14-19 May.

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Posted on 5 July 202129 February 2024