PMID- 31425781
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20200615
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
VI  - 144
IP  - 5
DP  - 2019 Nov
TI  - Long-term safety and pharmacodynamics of mepolizumab in children with severe 
      asthma with an eosinophilic phenotype.
PG  - 1336-1342.e7
LID - S0091-6749(19)31046-2 [pii]
LID - 10.1016/j.jaci.2019.08.005 [doi]
AB  - 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/muL at screening or >/=300 cells/muL 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.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Gupta, Atul
AU  - Gupta A
AD  - King's College Hospital NHS Foundation Trust, London, United Kingdom.
FAU - Ikeda, Masanori
AU  - Ikeda M
AD  - Department of Pediatric Acute Medicine, Okayama University Graduate School of 
      Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
FAU - Geng, Bob
AU  - Geng B
AD  - UCSD Division of Allergy & Immunology, Departments of Pediatrics and Medicine, 
      San Diego, Calif.
FAU - Azmi, Jay
AU  - Azmi J
AD  - Respiratory TAU, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
FAU - Price, Robert G
AU  - Price RG
AD  - Biostatistics, GlaxoSmithKline, Stevenage, United Kingdom.
FAU - Bradford, Eric S
AU  - Bradford ES
AD  - Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC.
FAU - Yancey, Steven W
AU  - Yancey SW
AD  - Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC.
FAU - Steinfeld, Jonathan
AU  - Steinfeld J
AD  - Respiratory TAU & Flexible Discovery Unit, GlaxoSmithKline, Philadelphia, Pa. 
      Electronic address: jonathan.x.steinfeld@gsk.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT02377427
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190816
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-5)
RN  - 90Z2UF0E52 (mepolizumab)
SB  - IM
MH  - Anti-Asthmatic Agents/therapeutic use
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Asthma/*drug therapy/epidemiology
MH  - Child
MH  - Disease Progression
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Eosinophilia/*drug therapy/epidemiology
MH  - Eosinophils/*immunology
MH  - Female
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Interleukin-5/antagonists & inhibitors
MH  - Leukocyte Count
MH  - Male
MH  - Phenotype
MH  - Severity of Illness Index
MH  - Time Factors
MH  - United States/epidemiology
OTO - NOTNLM
OT  - Pediatric asthma
OT  - eosinophilia
OT  - mepolizumab
EDAT- 2019/08/20 06:00
MHDA- 2020/06/17 06:00
CRDT- 2019/08/20 06:00
PHST- 2019/05/15 00:00 [received]
PHST- 2019/07/31 00:00 [revised]
PHST- 2019/08/12 00:00 [accepted]
PHST- 2019/08/20 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2019/08/20 06:00 [entrez]
AID - S0091-6749(19)31046-2 [pii]
AID - 10.1016/j.jaci.2019.08.005 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2019 Nov;144(5):1336-1342.e7. doi: 
      10.1016/j.jaci.2019.08.005. Epub 2019 Aug 16.