Frank C Albers1, Christopher Licskai2, Pascal Chanez3, Daniel J Bratton4, Eric S Bradford5, Steven W Yancey6, Namhee Kwon7, Santiago Quirce8. 1. Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA. Electronic address: frank-c.albers@t-online.de. 2. Department of Medicine, University of Western Ontario, London, ON, Canada; London Health Sciences, London, ON, Canada. Electronic address: Chris.Licskai@sjhc.london.on.ca. 3. Unités Mixtes de Recherche INSERM C2VN Center INSERM INRA UMR1062, Aix-Marseille Université, France; Department of Respiratory Diseases and Clinical Investigation Center, Assistance Publique-Hopitaux de Marseille, Hopital Nord, Marseille, France. Electronic address: Pascal.CHANEZ@univ-amu.fr. 4. Clinical Statistics, GSK, Stockley Park, Uxbridge, UK. Electronic address: daniel.x.bratton@gsk.com. 5. Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA. Electronic address: eric.s.bradford@gsk.com. 6. Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA. Electronic address: steve.w.yancey@gsk.com. 7. Respiratory Medical Franchise, GSK, Brentford, Middlesex, UK. Electronic address: namhee.n.kwon@gsk.com. 8. Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ), CIBER de Enfermedades Respiratorias CIBERES, Madrid, Spain. Electronic address: squirce@gmail.com.
Abstract
BACKGROUND: Previous analyses examining the relationship between blood eosinophil count and mepolizumab treatment effects in severe eosinophilic asthma have used a range of doses and administration routes. METHODS: This post hoc meta-analysis included data from the MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) trials. Patients (≥12 years) with severe eosinophilic asthma who experienced ≥2 exacerbations in the prior year received either mepolizumab 100 mg subcutaneously (SC) or 75 mg intravenously, or placebo plus standard of care every 4 weeks. This meta-analysis reports data from patients receiving the licensed dose of mepolizumab (100 mg SC) or placebo only. The primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints included rate of exacerbations requiring hospitalization/emergency room (ER) visit, proportion of patients with no clinically significant exacerbations, and changes from baseline in forced expiratory volume in 1 s, Asthma Control Questionnaire-5 and St George's Respiratory Questionnaire scores. Analyses were stratified by baseline blood eosinophil count (<150, ≥150, ≥300, ≥400, ≥500, ≥750, ≥1000, ≥150-<300, or ≥300-<500 cells/μL). RESULTS: Mepolizumab reduced annual clinically significant exacerbation rates by 45%-85%, exacerbations requiring hospitalization/ER visit by 60%-70%, and increased the odds of no clinically significant exacerbations across all eosinophil threshold subgroups versus placebo, and improved all other secondary endpoints in subgroups ≥150 cells/μL. Greater treatment effects with increasing blood eosinophil count were observed. CONCLUSIONS: Mepolizumab demonstrated consistent clinical benefits in patients with baseline blood eosinophil counts ≥150 cells/μL, confirming the suitability of this cut-off for identifying patients responsive to the licensed mepolizumab dose.
BACKGROUND: Previous analyses examining the relationship between blood eosinophil count and mepolizumab treatment effects in severe eosinophilic asthma have used a range of doses and administration routes. METHODS: This post hoc meta-analysis included data from the MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) trials. Patients (≥12 years) with severe eosinophilic asthma who experienced ≥2 exacerbations in the prior year received either mepolizumab 100 mg subcutaneously (SC) or 75 mg intravenously, or placebo plus standard of care every 4 weeks. This meta-analysis reports data from patients receiving the licensed dose of mepolizumab (100 mg SC) or placebo only. The primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints included rate of exacerbations requiring hospitalization/emergency room (ER) visit, proportion of patients with no clinically significant exacerbations, and changes from baseline in forced expiratory volume in 1 s, Asthma Control Questionnaire-5 and St George's Respiratory Questionnaire scores. Analyses were stratified by baseline blood eosinophil count (<150, ≥150, ≥300, ≥400, ≥500, ≥750, ≥1000, ≥150-<300, or ≥300-<500 cells/μL). RESULTS:Mepolizumab reduced annual clinically significant exacerbation rates by 45%-85%, exacerbations requiring hospitalization/ER visit by 60%-70%, and increased the odds of no clinically significant exacerbations across all eosinophil threshold subgroups versus placebo, and improved all other secondary endpoints in subgroups ≥150 cells/μL. Greater treatment effects with increasing blood eosinophil count were observed. CONCLUSIONS:Mepolizumab demonstrated consistent clinical benefits in patients with baseline blood eosinophil counts ≥150 cells/μL, confirming the suitability of this cut-off for identifying patients responsive to the licensed mepolizumab dose.
Authors: Namhee Kwon; Emilio Pizzichini; Aruna T Bansal; Frank C Albers; Neil Barnes; John H Rile; Aline Lima-Matos; Eduardo Viera Ponte; Alvaro A Cruz Journal: World Allergy Organ J Date: 2020-05-16 Impact factor: 4.084
Authors: Regina Maria de Carvalho-Pinto; José Eduardo Delfini Cançado; Marcia Margaret Menezes Pizzichini; Jussara Fiterman; Adalberto Sperb Rubin; Alcindo Cerci Neto; Álvaro Augusto Cruz; Ana Luisa Godoy Fernandes; Ana Maria Silva Araujo; Daniela Cavalet Blanco; Gediel Cordeiro Junior; Lilian Serrasqueiro Ballini Caetano; Marcelo Fouad Rabahi; Marcelo Bezerra de Menezes; Maria Alenita de Oliveira; Marina Andrade Lima; Paulo Márcio Pitrez Journal: J Bras Pneumol Date: 2021-12-15 Impact factor: 2.624
Authors: Marianne Baastrup Soendergaard; Susanne Hansen; Anne-Sofie Bjerrum; Ole Hilberg; Sofie Lock-Johansson; Kjell Erik Julius Håkansson; Truls Sylvan Ingebrigtsen; Claus Rikard Johnsen; Linda Makowska Rasmussen; Anna von Bülow; Karin Dahl Assing; Johannes Martin Schmid; Charlotte Suppli Ulrik; Celeste Porsbjerg Journal: ERJ Open Res Date: 2022-10-04
Authors: Tim Harrison; Giorgio Walter Canonica; Geoffrey Chupp; Jason Lee; Florence Schleich; Tobias Welte; Antonio Valero; Kim Gemzoe; Aoife Maxwell; Sandra Joksaite; Shibing Yang; Peter Howarth; Melissa K Van Dyke Journal: Eur Respir J Date: 2020-10-15 Impact factor: 16.671
Authors: Stefania Principe; Celeste Porsbjerg; Sisse Bolm Ditlev; Ditte Kjaersgaard Klein; Korneliusz Golebski; Nanna Dyhre-Petersen; Yoni E van Dijk; Job J M H van Bragt; Lente L H Dankelman; Sven-Erik Dahlen; Christopher E Brightling; Susanne J H Vijverberg; Anke H Maitland-van der Zee Journal: Clin Exp Allergy Date: 2021-05-21 Impact factor: 5.018