Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions

Respiratory Research

Elisabeth H. Bel¹  Stephen A. Mallett²  Mark Forshag³  Charlene M. Prazma⁴  Steve W. Yancey⁵  Steven G. Smith⁵  Eric S. Bradford⁵  Peter G. Gibson⁶  Geoffrey L. Chupp⁷ 

[1] Amsterdam University Medical Center, Location AMC, University of Amsterdam, Amsterdam, The Netherlands;Clinical Statistics, GSK, Stockley Park, Uxbridge, Middlesex, UK;Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA;Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA;GSK, PO Box 13398, 5 Moore Drive, 27709-3398, Research Triangle Park, NC, USA;Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA;School of Medicine and Public Health, University of Newcastle, Newcastle, Australia;Yale Center for Asthma and Airways Disease (YCAAD), Yale School of Medicine, New Haven, CT, USA;

关键词: Mepolizumab;    Severe eosinophilic asthma;    Comorbidities;    Upper respiratory;    Cardiovascular;    Treatable traits;   

DOI  :  10.1186/s12931-021-01746-4

来源: Springer

【 摘 要 】

BackgroundComorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities.MethodsThis was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline.ResultsOverall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup.ConclusionsMepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity.Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.

【 授权许可】

CC BY