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Gupta, Atul King's College Hospital NHS Foundation Trust
Ikeda, Masanori Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Geng, Bob UCSD Division of Allergy & Immunology, Departments of Pediatrics and Medicine
Azmi, Jay Respiratory TAU, GlaxoSmithKline
Price, Robert G. Biostatistics, GlaxoSmithKline
Bradford, Eric S.
Yancey, Steven W. Respiratory Therapeutic Area, GlaxoSmithKline
Steinfeld, Jonathan Respiratory TAU & Flexible Discovery Unit, GlaxoSmithKline
Background Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged 12 or more (United States) or 6 or more (European Union) years, but its long-term use in children aged 6 to 11 years has not yet been assessed. Objective We sought to assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6 to 11 years with severe asthma with an eosinophilic phenotype. Methods In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6 to 11 years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL in the previous year) received a body weight–dependent dose of subcutaneous mepolizumab of 40 mg (<40 kg) or 100 mg (≥40 kg) over 52 weeks. End points included the incidence of adverse events (AEs) and immunogenicity (primary), absolute blood eosinophil counts (cells per microliter; secondary), and annualized exacerbation rates and asthma control questionnaire/childhood asthma control test scores (exploratory). Results Over 52 weeks, 30 children received mepolizumab; 27 (90%) and 7 (23%) experienced on-treatment AEs and serious AEs, respectively. No serious AEs were treatment related. There were no fatal AEs. No specific patterns of AEs were evident, and no anti-drug antibody or neutralizing antibody responses were reported. Compared with baseline values, mepolizumab treatment reduced blood eosinophil counts and asthma exacerbations and improved asthma control across all treatment groups. Conclusion Long-term safety, pharmacodynamic, and efficacy data from this study support a positive benefit-risk profile for mepolizumab in children with severe asthma with an eosinophilic phenotype and were similar to data in studies in adults and adolescents.
Journal of Allergy and Clinical Immunology
© 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
Atul Gupta, Masanori Ikeda, Bob Geng, Jay Azmi, Robert G. Price, Eric S. Bradford, Steven W. Yancey, Jonathan Steinfeld, Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype, Journal of Allergy and Clinical Immunology, Volume 144, Issue 5, 2019, Pages 1336-1342.e7, ISSN 0091-6749, https://doi.org/10.1016/j.jaci.2019.08.005.