Treating severe paediatric asthma with mepolizumab or omalizumab: a protocol for the TREAT randomised non-inferiority trial.

Autor:	Cornelius V; Health and Social Care Research, Imperial College London, London, UK., Babalis D; Imperial Clinical Trials Unit, Imperial College London, London, UK.; Imperial College London School of Public Health, London, UK., Carroll WD; Academic Department of Child Health, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.; Institute of Applied Clinical Sciences, Keele University, Keele, UK., Cunningham S; Department of Child Life and Health, Royal Hospital for Sick Children, Edinburgh, UK., Fleming L; Royal Brompton Hospital and National Heart & Lung Institute, Imperial College London, London, UK., Gaillard E; Leicester NIHR Biomedical Research Centre (Respiratory Theme), Leicester, Leicestershire, UK.; Paediatric Clinical Investigation Centre, Leicester, UK., Gupta A; King's College Hospital Foundation Trust, London, UK., Janani L; Faculty of Medicine, Imperial College London, London, UK., Kennington E; Asthma and Lung UK, London, UK., Murray C; Division of Immunology, Immunity to Infection and Respiratory Medicine (DIIIRM), School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Nagakumar P; Institute of Inflammation and Aging, Birmingham Women's and Children's Hospitals NHS Foundation Trust, Birmingham, UK.; University of Birmingham, Birmingham, UK., Roberts G; Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.; Respiratory Biomedical Research Unit, Southampton University Hospitals Trust, Southampton, UK., Seddon P; Brighton and Sussex Medical School, Brighton, UK., Sinha I; Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK., Streatfield C; Faculty of Medicine, Imperial College London, London, UK., Weir E; Royal Hospital for Children, Glasgow, UK., Saglani S; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK s.saglani@imperial.ac.uk.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2024 Aug 21; Vol. 14 (8), pp. e090749. Date of Electronic Publication: 2024 Aug 21.
DOI:	10.1136/bmjopen-2024-090749
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Databáze:	MEDLINE
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