start-ver=1.4 cd-journal=joma no-vol=144 cd-vols= no-issue=5 article-no= start-page=1336 end-page=1342 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=Gupta Atul en-aut-sei=Gupta en-aut-mei= Atul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Ikeda Masanori en-aut-sei=Ikeda en-aut-mei= Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Geng Bob en-aut-sei=Geng en-aut-mei= Bob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Azmi Jay en-aut-sei=Azmi en-aut-mei= Jay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Price Robert G. en-aut-sei=Price en-aut-mei= Robert G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Bradford Eric S. en-aut-sei=Bradford en-aut-mei= Eric S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Yancey Steven W. en-aut-sei=Yancey en-aut-mei= Steven W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Steinfeld Jonathan en-aut-sei=Steinfeld en-aut-mei= Jonathan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=King's College Hospital NHS Foundation Trust kn-affil= affil-num=2 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=UCSD Division of Allergy & Immunology, Departments of Pediatrics and Medicine kn-affil= affil-num=4 en-affil=Respiratory TAU, GlaxoSmithKline kn-affil= affil-num=5 en-affil=Biostatistics, GlaxoSmithKline kn-affil= affil-num=6 en-affil= kn-affil= affil-num=7 en-affil=Respiratory Therapeutic Area, GlaxoSmithKline kn-affil= affil-num=8 en-affil=Respiratory TAU & Flexible Discovery Unit, GlaxoSmithKline kn-affil= en-keyword=Pediatric asthma kn-keyword=Pediatric asthma en-keyword=eosinophilia kn-keyword=eosinophilia en-keyword=mepolizumab kn-keyword=mepolizumab END