Montelukast Eases Asthma Symptoms in Youngest Patients

Takao Fujisawa, MD, PhD

Preschool children who received daily montelukast (Singulair) experienced fewer asthma symptom exacerbations than those receiving an as-needed beta 2-agonist bronchodilator, in a randomized controlled trial of treatment for early stage asthma.

The study was conducted in Japan, where guidelines indicate asthma control medication for an earlier stage than in the West, according to Takao Fujisawa, MD, PhD, Vice Dean, Faculty of Medicine, Tokohu Medical and Pharmaceutical University, Sendai, Japan and colleagues.

In contrast to the Global Initiative for Asthma (GINA) and the National Asthma Education and Prevention Program's Expert Panel Reports 3 (EPR-3) indicating medication for mild, persistent asthma corresponding to symptoms that occur more than weekly but less than daily, the Japanese guideline for child asthma (JGCA) indicates control medication for symptoms occurring more than monthly, but less than weekly.

"As a result, JGCA recommends starting control treatment in earlier disease stage," researchers wrote. "In addition, JGCA includes leukotriene antagonists in controller medication, whereas the GINA report and EPR-3 recommend inhaled corticosteroids (ICSs) as the most effective controller medication."

Researchers suggested that montelukast, a leukotriene antagonist, could provide particular advantage in treating preschool children.

"Starting control treatment in early disease stage may help prevent acute exacerbations and disease progression," they wrote. "Although the benefits of ICSs in patients with persistent asthma have been well established, their early use in preschool children had no effect on the natural history of asthma."

To evaluate the benefit of a daily montelukast regimen in preschool children with asthma symptoms occurring less than once a week, the investigators randomized 93 patients aged 1 to 5 years in a 1:1 ratio to 48 weeks of treatment with either montelukast or an as-need beta 2-agonist bronchodilator.

The primary endpoint was the number of acute asthma exacerbations before requiring step-up treatment with an ICS. Secondary endpoints included time to the first onset of acute asthma exacerbation, time to the start of step-up treatment, and the number of symptom-free days.

The investigators reported that fewer patients in the montelukast group than in the as-need bronchodilator group experienced acute exacerbations (23% vs 50%), and that 21% of the montelukast group compared to 41% of the bronchodilator group required step-up treatment. The cumulative incidence of step-up treatment was also significantly lower in the montelukast group (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.21-0.92). They also wrote that montelukast was well tolerated, with most adverse events unrelated to the medication.

"Our result indicated that montelukast prevented disease progression in younger children and that control treatment should be started in earlier disease stage," Fujisawa and colleagues concluded.

The optimal control treatment remains to be determined, however, as the researchers compared the montelukast control regimen to a no-control, as-needed treatment.

In a meta-analysis published in the June 2016 Pediatrics, Michael Cabana, MD, MPH, University of California, San Francisco and colleagues considered the evidence for several treatments in preventing severe exacerbations among preschool children with recurrent wheeze.

"Therapeutic decisions remain challenging until more studies are conducted that clearly describe the disease pattern and baseline risk of enrolled children and directly compare daily ICS, intermittent ICS, and montelukast," Cabana and colleagues wrote.

The study, “Early control treatment with montelukast in preschool children with asthma: A randomized controlled trial,” was published in Allergology International.