Mepolizumab reduces exacerbations in youths with eosinophilic asthma living in urban areas

Phenotype-directed mepolizumab therapy reduced the number of asthma exacerbations among children and adolescents with exacerbation-prone eosinophilic asthma who live in disadvantaged urban neighborhoods, researchers reported in The Lancet.

“[I]n urban children and adolescents with exacerbation-prone eosinophilic asthma, adjunctive therapy with mepolizumab reduced asthma exacerbations, but did not affect other asthma outcomes,” Daniel J. Jackson, MD, associate professor in the departments of pediatrics and medicine at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues wrote.

The randomized, double-blind, placebo-controlled, parallel-group MUPPITS-2 trial included 290 children and adolescents (57% boys) from nine urban medical centers in the U.S. from November 2017 to March 2020. All participants lived in socioeconomically disadvantaged neighborhoods and had exacerbation-prone asthma, which was defined as two or more exacerbations in the past year with blood eosinophils of at least 150 cells/µL. Participants were randomly assigned to mepolizumab (Nucala, GlaxoSmithKline) at 40 mg for those aged 6 to 11 years and 100 mg for those aged 12 to 17 years (n = 146) or placebo (n = 144) once every 4 weeks plus guideline-based care for 52 weeks.

The primary outcome was number of asthma exacerbations treated with systemic corticosteroids during the study period.

Overall, 248 children and adolescents completed the study.

The mean number of asthma exacerbations was 0.96 among those assigned mepolizumab and 1.3 among those assigned placebo (RR = 0.73; 95% CI, 0.56-0.96; P = .027). Time to first asthma exacerbation was not significantly different between the two groups (HR = 0.86; 95% CI, 0.63-1.18; P = .36).

By the end of the study period, 84% of participants treated with mepolizumab and 89% of participants treated with placebo self-reported clinically moderate or significant disease improvements through the patient global assessment (OR = 0.72; 95% CI, 0.42-1.24; P = .24). When study clinicians completed the same assessment, they found clinically moderate or significant improvement among 66% of participants treated with mepolizumab and 71% of participants treated with placebo (OR = 1.01; 95% CI, 0.62-1.64; P = .97).

Treatment-emergent adverse events occurred in 29% of participants assigned mepolizumab compared with 11% assigned placebo. The most common adverse events were injection-site reactions (13% vs. 5%) and skin and subcutaneous tissue disorders (7% vs. < 1%) among the mepolizumab and placebo groups. Researchers reported no deaths attributed to mepolizumab treatment during the treatment period.

“Our findings also highlight the importance of evaluating treatment responses for biologics, and other interventions, in urban Black and Hispanic children, populations often underrepresented in clinical trials and at greatest risk for morbidity and mortality from asthma,” the researchers wrote.