IL-4/IL-13 blockade successful in children with uncontrolled moderate-to-severe asthma

The LIBERTY ASTHMA VOYAGE study demonstrated that dupilumab reduces annualised exacerbations in children with uncontrolled moderate-to-severe asthma by more than 50% compared with placebo.

Despite optimised standard-of-care therapy, children with moderate-to-severe asthma may continue to have uncontrolled disease. The IL-4/IL-13 blocker dupilumab has previously been shown to be effective and has a demonstrated safety profile in adolescents and adults with moderate-to-severe asthma, patients aged ≥6 years with moderate-to-severe atopic dermatitis, and adults with chronic rhinosinusitis with nasal polyps. As Prof. Leonard B. Bacharier (Vanderbilt University Medical Center, Tennessee, USA) pointed out during the presentation of the LIBERTY ASTHMA VOYAGE (NCT02948959) results, type 2 inflammation underlies most cases of asthma in children and is characterised by release of signature cytokines IL-4, IL-5, and IL-13 [1].

The LIBERTY ASTHMA VOYAGE trial tried to assess the efficacy of the monoclonal antibody in children aged 6–11 with uncontrolled moderate-to-severe asthma. Enrolled in the trial were 408 children. Patients receiving high-dose inhaled corticosteroids alone or medium-to-high dose inhaled corticosteroids with a second asthma controller were randomised in a 2:1 ratio to either receive 100 mg or 200 mg subcutaneous dupilumab or a matched placebo for up to 52 weeks.

In LIBERTY ASTHMA VOYAGE, pre-specified primary analyses were performed in 2 study populations: 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 64% in the population with baseline blood eosinophils ≥300 cells/μl. In addition, treatment improved the percentage of predicted pre-bronchodilator first second of forced expiratory volume at week 12, a key secondary endpoint, in both populations and reduced FeNO significantly at 12 weeks compared with placebo. Dupilumab 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 compared with placebo, as assessed with the Asthma Control Questionnaire Interviewer Administered.

Dupilumab demonstrated an acceptable safety profile. Safety results were 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 them enterobiasis, but they were not serious and did not lead to treatment discontinuation,” Prof. Bacharier explained. Median blood eosinophil values decreased to below the baseline level by the 52^nd week in the dupilumab group.

“The effect of dupilumab on improving lung function in these children was particularly impressive,” noted Prof. 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. 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.

Posted on 20 May 20214 August 2021