麻豆传媒

PHOENIX -- Adding mepolizumab (Nucala) to guideline-based care reduced flare-ups in disadvantaged kids with exacerbation-prone, eosinophilic asthma, the yearlong showed.

In the randomized study of nearly 300 kids living in urban parts of the U.S., the annualized exacerbation rate was 0.96 with mepolizumab versus 1.30 with placebo, representing a 27% relative decrease (rate ratio 0.73, 95% CI 0.56-0.96, P=0.03), reported Daniel Jackson, MD, of the University of Wisconsin in Madison.

While the trial met its primary endpoint, there were no differences in various secondary endpoints, including time to first exacerbation, Composite Asthma Severity Index (CASI) scores, or lung function outcomes, he said here at the annual meeting of the American Academy of Allergy, Asthma & Immunology.

Treatment-emergent adverse events were higher with mepolizumab (28.5% vs 11% with placebo), with the main problem cited being injection-site reactions.

The interleukin (IL)-5 targeting biologic mepolizumab has been shown to be effective at controlling asthma in adults, but to-date data in children have been limited, said Jackson.

The (Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2) trial enrolled 290 children ages 6 to 17 and randomized them to guideline-based asthma management for 52 weeks plus either mepolizumab (subcutaneously every 4 weeks; n=146) or matching placebo (n=144).

Participants were eligible if they lived in an urban setting, had experienced at least two severe asthma exacerbations in the previous year, and were found to have eosinophil levels of at least 150 cells/µl.

Children in the study had a median age of 10 years, about 55% were boys, roughly 70% were Black, and one-fourth were Hispanic. Most of the households had median incomes of $1,250 or below per month (37-40%) or ranging from $1,251 to $2,500 per month (32-37%). More than a quarter of the kids lived in household with current smokers.

In the study, mepolizumab rapidly and markedly reduced blood eosinophil levels, from over 400 cells/µl at baseline to less than 200 cells/µl by week 8, which was sustained through the yearlong trial. Eosinophil levels remained constantly over 400 cells/µl in the placebo-treated children. There was also a similar reduction in airway eosinophils with mepolizumab, Jackson noted.

"This study gives us one more piece to the puzzle of the total picture for our patients and how we want to be directing our efforts in getting at underlying symptom drivers," said William Anderson, MD, of Children's Hospital Colorado and the University of Colorado in Aurora.

"Potentially, we are not necessarily looking at the full mechanism of what is truly exacerbating pediatric asthma," he told 麻豆传媒. "While exacerbation may be one component of it -- the eosinophils -- you aren't necessarily hitting the other markers or causes that might be contributing to the underlying cause of asthma."

Anderson, who was not involved in the research, noted that with so many different biologics on the market, and more and more gaining indications for pediatric patients, "we need to lay out the risk and benefits of the possible treatments."

Effects on exacerbations will be one factor that people look at, but secondary measures such as daily symptoms and CASI scores will be considered in as well, he said.

"So this drug will treat exacerbations, but if you were looking to improve lung function, maybe this would not be the best choice," he said.

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