PMID- 27553751
OWN - NLM
STAT- MEDLINE
DCOM- 20171010
LR  - 20220410
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 38
IP  - 9
DP  - 2016 Sep
TI  - Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic 
      Asthma: A Multi-center, Open-label, Phase IIIb Study.
PG  - 2058-2070.e1
LID - S0149-2918(16)30453-2 [pii]
LID - 10.1016/j.clinthera.2016.07.010 [doi]
AB  - PURPOSE: Patients with severe eosinophilic asthma often experience recurrent 
      asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 
      previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), 
      treatment with intravenous or subcutaneous mepolizumab was associated with 
      significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) 
      requirements compared with placebo. The purpose of this study was to assess the 
      long-term safety and efficacy of subcutaneous mepolizumab treatment in patients 
      with severe eosinophilic asthma. METHODS: COSMOS was a 52-week, open-label 
      extension study in patients who received mepolizumab or placebo in MENSA or 
      SIRIUS. Patients received subcutaneous mepolizumab regardless of prior treatment 
      allocation and continued to receive appropriate standard-of-care asthma therapy 
      throughout. The primary objective was to assess the long-term safety of 
      mepolizumab; end points included adverse events (AEs) and serious AEs (SAEs). 
      Efficacy assessments included the annualized exacerbation rate and durability of 
      response (defined as the exacerbation rate and OCS dose reduction when combined 
      with MENSA and SIRIUS data, respectively). FINDINGS: In total, 558 (86%; previous 
      mepolizumab: 358; previous placebo: 200) and 94 (14%; previous mepolizumab: 58, 
      previous placebo: 36) patients experienced on-treatment AEs and SAEs, 
      respectively. No fatal AEs were reported. Totals of 13 (2%) and 29 (4%) patients 
      experienced systemic and local site reactions, respectively. There were no 
      reports of mepolizumab-related anaphylaxis. Mepolizumab treatment was shown to 
      exert a durable response, with patients who previously received mepolizumab in 
      MENSA or SIRIUS maintaining reductions in exacerbation rate and OCS dosing 
      throughout COSMOS. Patients who previously received placebo in MENSA or SIRIUS 
      demonstrated improvements in these end points following treatment with 
      mepolizumab in COSMOS. IMPLICATIONS: These data demonstrate a favorable safety 
      profile of mepolizumab and indicate a durable and stable effect over time, 
      supporting long-term treatment in patients with severe eosinophilic asthma. 
      ClinicalTrials.gov identifier: NCT01842607.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Lugogo, Njira
AU  - Lugogo N
AD  - Duke Asthma, Allergy and Airway Center, Duke Medicine, Durham, North Carolina.
FAU - Domingo, Christian
AU  - Domingo C
AD  - Corporacio Sanitaria Parc Tauli, Universitat Autonoma de Barcelona, Barcelona, 
      Spain.
FAU - Chanez, Pascal
AU  - Chanez P
AD  - Respiratory Medicine, Inserm U1067, Aix-Marseille University, Marseille, France.
FAU - Leigh, Richard
AU  - Leigh R
AD  - Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, 
      Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
FAU - Gilson, Martyn J
AU  - Gilson MJ
AD  - Respiratory Therapeutic Area, GlaxoSmithKline, Stockley Park, Uxbridge, United 
      Kingdom.
FAU - Price, Robert G
AU  - Price RG
AD  - Clinical Statistics, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
FAU - Yancey, Steven W
AU  - Yancey SW
AD  - Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North 
      Carolina. Electronic address: steve.w.yancey@gsk.com.
FAU - Ortega, Hector G
AU  - Ortega HG
AD  - Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North 
      Carolina.
LA  - eng
SI  - ClinicalTrials.gov/NCT01842607
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160821
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Glucocorticoids)
RN  - 90Z2UF0E52 (mepolizumab)
SB  - IM
MH  - Administration, Intravenous
MH  - Adrenal Cortex Hormones/therapeutic use
MH  - Anti-Asthmatic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Asthma/*drug therapy
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Eosinophilia/drug therapy
MH  - Female
MH  - Glucocorticoids/administration & dosage
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Young Adult
OTO - NOTNLM
OT  - *durability
OT  - *exacerbations
OT  - *mepolizumab
OT  - *safety
OT  - *severe eosinophilic asthma
EDAT- 2016/08/25 06:00
MHDA- 2017/10/11 06:00
CRDT- 2016/08/25 06:00
PHST- 2016/05/19 00:00 [received]
PHST- 2016/07/08 00:00 [revised]
PHST- 2016/07/20 00:00 [accepted]
PHST- 2016/08/25 06:00 [entrez]
PHST- 2016/08/25 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
AID - S0149-2918(16)30453-2 [pii]
AID - 10.1016/j.clinthera.2016.07.010 [doi]
PST - ppublish
SO  - Clin Ther. 2016 Sep;38(9):2058-2070.e1. doi: 10.1016/j.clinthera.2016.07.010. 
      Epub 2016 Aug 21.