Mepolizumab Reduces Exacerbations in Urban Children With Eosinophilic Asthma

Beautiful Girl With Respiratory System Problems is Using an Asthma Inhaler Outdoors in a Park.
Can adding mepolizumab to guideline-based care reduce asthma exacerbations in economically disadvantaged urban children with eosinophilic asthma?

In urban children and adolescents with exacerbation-prone eosinophilic asthma, adjunctive treatment with mepolizumab is associated with reduced exacerbations but does not affect other disease outcomes, according to clinical trial results published in The Lancet.

Treatments directed at the eosinophilic phenotype have been linked to reduced asthma exacerbations in adults; however, scant data are available regarding use of this therapy in children and diverse populations. To determine whether such phenotype-directed therapy with mepolizumab reduced exacerbations in economically disadvantaged urban children, researchers conducted a clinical trial to determine whether mepolizumab, when added to guideline-based care, reduced the number of asthma exacerbations in an urban pediatric patients during a 52-week period. The researchers also hoped to gain insight into the clinical and mechanistic effects of mepolizumab.

The randomized, double-blind, placebo-controlled, parallel-group MUPPITS-2 trial ( identifier: NCT03292588) involved 290 children and adolescents 6 to 17 years of age, recruited at 9 US urban medical centers between November 2017 and March 2020, who lived in socioeconomically disadvantaged urban neighborhoods. Patients had exacerbation-prone asthma (which was defined as ≥2 exacerbations in the prior year) and blood eosinophil counts of 150 cells/μL or less. The patients were randomly assigned in a 1:1 ratio to receive mepolizumab (40 mg in 6- to 12-year-olds; 100 mg in 12- to 17-year-olds; n=146) or placebo injections (n=144) once every 4 weeks, plus guideline-based care, for 52 weeks.

The primary study outcome was the number of asthma exacerbations that were treated with systemic corticosteroids over 52 weeks in the intention-to-treat population. Secondary outcome measures included the time to first asthma exacerbation, changes in Composite Asthma Severity Index score, physician-patient global assessment of response to treatment since study initiation, and lung function (measured via forced expiratory volume in 1 second % predicted).

A total of 248 patients completed the study. Results showed that the mean number of asthma exacerbations within the 52-week study period was 0.96 (95% CI, 0.78-1.17) with mepolizumab compared with 1.30 (95% CI, 1.08-1.57) with placebo (rate ratio, 0.73; 95% CI, 0.56-0.96; P =.27). No deaths were associated with mepolizumab use. Treatment-emergent adverse events were reported in 29% of patients in the mepolizumab arm and 11% of those in the placebo arm.

Study limitations included the use of nasal airway samples as a proxy for lower airway disease and the fact that exacerbation frequency was affected by the COVID-19 pandemic.

The researchers concluded that their findings highlighted “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 research also showed that “airway transcriptomic profiling provides detailed molecular insights into treatment response and non-response, thereby identifying essential novel biomarkers and disease mechanisms.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Jackson DJ, Bacharier LB, Gergen PJ, et al; US National Institute of Allergy and Infectious Disease’s Inner City Asthma Consortium. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet. 2022;400(10351):502-511. doi:10.1016/S0140-6736(22)01198-9