Inflammatory Pathways in Residual Asthma Exacerbations Among Mepolizumab-Treated Urban Children: A Secondary Analysis of a Randomized Clinical Trial
Abstract
Importance
While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined.
Objective
To identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab vs placebo.
Design, Setting, and Participants
This is a secondary analysis of the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (MUPPITS-2) double-blind, placebo-controlled, parallel-group, randomized clinical trial comparing treatment with mepolizumab vs placebo among children with exacerbation-prone asthma in low-income urban centers in 9 US cities. Data analysis was performed from September 2022 to April 2025.
Intervention
Participants were randomized to receive either mepolizumab (aged 6-11 years: 40 mg; aged 12-17 years: 100 mg) or matching placebo by subcutaneous injection once every 4 weeks for 52 weeks.
Main Outcomes and Measures
The primary measurement was a transcriptomic modular analysis by RNA sequencing of nasal samples obtained during acute respiratory illnesses. Associations among upper airway transcriptional signatures, the clinical outcome of respiratory illnesses, and pulmonary functions were investigated.…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 290 participants or records.
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