@article{c6d63a8a9f7c47b8aa82a2aed33283f6,
title = "Rapid and Consistent Improvements in Morning PEF in Patients with Severe Eosinophilic Asthma Treated with Mepolizumab",
abstract = "Introduction: Previous studies showed that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. However, early studies reported inconsistent effects on lung function. This study specifically assessed the onset of clinical effect and the relationship of baseline blood eosinophil count of mepolizumab 100 mg subcutaneous (SC) administration on morning peak expiratory flow (AM PEF). Methods: Post hoc analysis of data from two randomized, double-blind, placebo-controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma. Individual study results were generated using a mixed model repeated measures model controlling for multiple covariates and were combined using a fixed effects meta-analysis via inverse-variance weighting. Results: Significant improvements in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as early as week 1 and continued to improve further with subsequent doses. The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p < 0.001. When the population was stratified by blood eosinophil thresholds the mean difference from placebo was 24 L/min (≥ 150 cells/µL), 27 L/min (≥ 300 cells/µL), and 34 L/min (≥ 500 cells/µL), p < 0.001 for all subgroups. The < 150 cells/µL (≥ 300 cells/µL in the previous year) group increased 13 L/min, while both 150 to < 300 cells/µL and 300 to < 500 cells/µL ranges demonstrated comparable changes (19 L/min and 17 L/min), respectively. Conclusion: Our analysis has shown early and consistent improvements in lung function measured by AM PEF using the study enrollment criterion of ≥ 150 eosinophils/µL. We also identified a relationship between baseline blood eosinophils and improvements in AM PEF with mepolizumab in patients with severe eosinophilic asthma. Funding: GlaxoSmithKline (study ID 208091).",
keywords = "AM PEF, Anti-IL-5, Blood eosinophils, Lung function, Monoclonal antibody, Respiratory, Severe asthma",
author = "Hector Ortega and Andrew Menzies-Gow and Llanos, {Jean Pierre} and Mark Forshag and Frank Albers and Necdet Gunsoy and Bradford, {Eric S.} and Yancey, {Steven W.} and Monica Kraft",
note = "Funding Information: Editorial Assistance. Editorial support (in the form of formatting and grammatical editing) was provided by Susan Parker, PhD, of Fishawack Indicia Ltd, Oxford, UK funded by GSK. Funding Information: Funding. The study, the article processing charges, and the Open Access fee were funded by GlaxoSmithKline (study ID 208091). Funding Information: The study, the article processing charges, and the Open Access fee were funded by GlaxoSmithKline (study ID 208091). Editorial support (in the form of formatting and grammatical editing) was provided by Susan Parker, PhD, of Fishawack Indicia Ltd, Oxford, UK funded by GSK. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Conception and design: HO, AM-G, J-PL, MF, FA, NG, EB, SY, and MK; Acquisition of data: HO, FA, NG, EB, SY; Data analysis and interpretation: HO, AM-G, J-PL, MF, FA, NG, EB, SY, and MK. The first draft was written by the lead author, HO. All authors were involved in development of all stages of the manuscript, revising it critically for important intellectual content. All authors provided final approval of the version submitted for publication. All authors are accountable for the accuracy and integrity of the work. Hector Ortega is an employee of GSK and owns stock/stock options in GSK. Jean-Pierre Llanos is an employee of GSK and owns stock/stock options in GSK. Mark Forshag is an employee of GSK and owns stock/stock options in GSK. Frank Albers is an employee of GSK and owns stock/stock options in GSK. Necdet Gunsoy is an employee of GSK and owns stock/stock options in GSK. Eric S Bradford is an employee of GSK and owns stock/stock options in GSK. Steven W Yancey is an employee of GSK and owns stock/stock options in GSK. Andrew Menzies-Gow has attended advisory boards with GSK, AstraZeneca, Novartis, Hoffman La Roche, Boehringer Ingelheim, and Teva. He has received lecture fees from Novartis, Vectura, Napp, AstraZeneca, Boehringer Ingelheim, and Teva. He has attended international conferences with AstraZeneca, Napp, and Boehringer Ingelheim. He has participated in clinical trials with GSK, AstraZeneca, Boehringer Ingelheim, and Hoffman La Roche and has consultancy agreements with AstraZeneca and Vectura. Monica Kraft has received research funding (paid to University of Arizona) from Chiesi, Sanofi, and Genentech/Roche. She has attended advisory boards with AstraZeneca, Teva, and Regeneron. The studies were conducted in accordance with the ethical principles of the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice (GCP), and the applicable country-specific regulatory requirements. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. To view enhanced digital features for this article go to 10.6084/m9.figshare.6384596. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = jul,
day = "1",
doi = "10.1007/s12325-018-0727-8",
language = "English (US)",
volume = "35",
pages = "1059--1068",
journal = "Advances in Therapy",
issn = "0741-238X",
publisher = "Health Communications Inc.",
number = "7",
}