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Treating severe paediatric asthma with mepolizumab or omalizumab: a protocol for the TREAT randomised non-inferiority
Victoria Cornelius1, Daphne Babalis2,3, William D Carroll4,5
1Health and Social Care Research, Imperial College London, London, UK.
Insights
This trial compares mepolizumab to omalizumab for severe pediatric asthma. It assesses if mepolizumab is as effective as omalizumab in reducing asthma attacks in children with difficult-to-treat asthma.
Area of Science:
- Pediatric Pulmonology
- Clinical Immunology
- Pharmacotherapy
Background:
- Severe pediatric asthma affects a minority of children, leading to high morbidity and mortality despite maximal therapy.
- Omalizumab, a biologic targeting immunoglobulin E (IgE), was the first approved therapy for severe pediatric asthma, but response rates vary.
- Mepolizumab, a biologic targeting interleukin-5 (IL-5), is approved for adults and by extrapolation for children, but its efficacy compared to omalizumab in pediatric populations requires direct investigation.
Purpose of the Study:
- To conduct a non-inferiority trial comparing mepolizumab and omalizumab in children with severe therapy-resistant asthma (STRA) and refractory difficult asthma (DA).
- To determine if mepolizumab is as efficacious as omalizumab in reducing asthma attack rates in this pediatric population.
- To explore secondary outcomes including asthma severity, quality of life, lung function, and biomarkers predictive of treatment response.
Main Methods:
- An ongoing, multicenter, randomized, non-inferiority, open-label trial involving up to 150 children and young people (CYP) aged 6-17 years in the UK.
- Participants undergo a 16-week monitoring period for medication adherence to confirm STRA and refractory DA diagnoses prior to randomization.
- The primary outcome is the 52-week asthma attack rate, analyzed using Bayesian methods to assess non-inferiority. Secondary outcomes are analyzed using frequentist methods.
Main Results:
- This section is not yet available as the trial is ongoing.
- Data collection and analysis for primary and secondary outcomes are in progress.
- The study is designed to provide robust evidence on the comparative efficacy of two leading biologic therapies for severe pediatric asthma.
Conclusions:
- This non-inferiority trial is crucial for establishing the efficacy of mepolizumab relative to omalizumab in children with severe, difficult-to-treat asthma.
- Findings will inform clinical practice and treatment guidelines for managing this vulnerable patient group.
- The study will also identify potential biomarkers to personalize biologic therapy selection for improved outcomes in pediatric asthma.
Introduction:
A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA).
Methods And Analysis:
This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6-17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models.
Ethics And Dissemination:
The study has been approved by the South Central-Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners.
Trial Registration Number:
ISRCTN12109108; EudraCT Number: 2019-004085-17.
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