Response to mepolizumab treatment is sustained across 4-weekly dosing periods

Background Mepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. How...

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Main Authors: Ian D. Pavord, Eugene R. Bleecker, Roland Buhl, Pascal Chanez, Elisabeth H. Bel, Peter Howarth, Daniel J. Bratton, Frank C. Albers, Steven Yancey
Format: Article
Language:English
Published: European Respiratory Society 2020-09-01
Series:ERJ Open Research
Online Access:http://openres.ersjournals.com/content/6/3/00068-2020.full
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spelling doaj-d061689a1e2545f094dab881d225191f2020-11-25T02:48:10ZengEuropean Respiratory SocietyERJ Open Research2312-05412020-09-016310.1183/23120541.00068-202000068-2020Response to mepolizumab treatment is sustained across 4-weekly dosing periodsIan D. Pavord0Eugene R. Bleecker1Roland Buhl2Pascal Chanez3Elisabeth H. Bel4Peter Howarth5Daniel J. Bratton6Frank C. Albers7Steven Yancey8 Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Dept of Medicine, University of Oxford, Oxford, UK Genomics and Precision Medicine, University of Arizona College of Medicine, Tucson, AZ, USA Dept of Pulmonary Medicine, Mainz University Hospital, Mainz, Germany Clinique des bronches allergies et sommeil, INSERM C2VN Center and CIC Nord APHM, Aix-Marseille University, Marseille, France Dept of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands Global Medical Franchise, GSK, Brentford, UK Clinical Statistics, GSK, Stockley Park, UK Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA Background Mepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses. Methods This was a post hoc analysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophilic asthma were randomised (1:1:1:1) to receive intravenous mepolizumab 75 mg (equivalent to 100 mg s.c.), 250 mg, 750 mg or placebo, plus standard of care, every 4 weeks for 52 weeks. The number of exacerbations and eDiary data (peak expiratory flow, rescue medication use and symptom scores) from two periods in each 4-weekly dosing interval (days 1–14 and 15–28) over the 52-week treatment period were analysed. Findings eDiary data and the proportion of patients experiencing ≥1 exacerbation were similar during the first and second 2 weeks of a dosing period across all mepolizumab doses. Interpretation These results demonstrate that the response to mepolizumab is sustained over the 4-weekly dosing period with no differences across a 10-fold dose range and supports the use of the current mepolizumab dosing regimen in patients with severe eosinophilic asthma.http://openres.ersjournals.com/content/6/3/00068-2020.full
collection DOAJ
language English
format Article
sources DOAJ
author Ian D. Pavord
Eugene R. Bleecker
Roland Buhl
Pascal Chanez
Elisabeth H. Bel
Peter Howarth
Daniel J. Bratton
Frank C. Albers
Steven Yancey
spellingShingle Ian D. Pavord
Eugene R. Bleecker
Roland Buhl
Pascal Chanez
Elisabeth H. Bel
Peter Howarth
Daniel J. Bratton
Frank C. Albers
Steven Yancey
Response to mepolizumab treatment is sustained across 4-weekly dosing periods
ERJ Open Research
author_facet Ian D. Pavord
Eugene R. Bleecker
Roland Buhl
Pascal Chanez
Elisabeth H. Bel
Peter Howarth
Daniel J. Bratton
Frank C. Albers
Steven Yancey
author_sort Ian D. Pavord
title Response to mepolizumab treatment is sustained across 4-weekly dosing periods
title_short Response to mepolizumab treatment is sustained across 4-weekly dosing periods
title_full Response to mepolizumab treatment is sustained across 4-weekly dosing periods
title_fullStr Response to mepolizumab treatment is sustained across 4-weekly dosing periods
title_full_unstemmed Response to mepolizumab treatment is sustained across 4-weekly dosing periods
title_sort response to mepolizumab treatment is sustained across 4-weekly dosing periods
publisher European Respiratory Society
series ERJ Open Research
issn 2312-0541
publishDate 2020-09-01
description Background Mepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses. Methods This was a post hoc analysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophilic asthma were randomised (1:1:1:1) to receive intravenous mepolizumab 75 mg (equivalent to 100 mg s.c.), 250 mg, 750 mg or placebo, plus standard of care, every 4 weeks for 52 weeks. The number of exacerbations and eDiary data (peak expiratory flow, rescue medication use and symptom scores) from two periods in each 4-weekly dosing interval (days 1–14 and 15–28) over the 52-week treatment period were analysed. Findings eDiary data and the proportion of patients experiencing ≥1 exacerbation were similar during the first and second 2 weeks of a dosing period across all mepolizumab doses. Interpretation These results demonstrate that the response to mepolizumab is sustained over the 4-weekly dosing period with no differences across a 10-fold dose range and supports the use of the current mepolizumab dosing regimen in patients with severe eosinophilic asthma.
url http://openres.ersjournals.com/content/6/3/00068-2020.full
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