Journal of Asthma and Allergy (Jun 2021)
Response to Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma and Atopic Phenotypes
Abstract
Charlene M Prazma,1 Marco Idzko,2,3 Jo Anne Douglass,4 Arnaud Bourdin,5,6 Stephen Mallett,7 Frank C Albers,8 Steven W Yancey1 1Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA; 2Division of Pneumology, Medical University of Vienna, Vienna, Austria; 3Department of Pneumology, University Hospital Freiburg, Freiburg, Germany; 4The Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia; 5Departement de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France; 6PhyMedExp, University of Montpellier, Montpellier, France; 7Clinical Statistics, GSK, Uxbridge, Middlesex, UK; 8Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USACorrespondence: Charlene M PrazmaRespiratory Therapeutic Area, GSK, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC, 27709, USATel +1 919 483 9013Email [email protected]: Improved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions.Patients and Methods: This was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥ 12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (< 150, ≥ 150– 300, ≥ 300 cells/μL) within atopic subgroups (non-atopic [specific immunoglobulin E < 0.35 kU/L], atopic [≥ 0.35– 17.5 kU/L], strongly atopic [> 17.5 kU/L]), and by house dust mite (HDM) sensitivity.Results: Of 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥ 300 cells/μL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of < 150 cells/μL. Improvements in ACQ-5 scores of – 0.75, – 0.73 and – 0.78 with mepolizumab versus placebo were observed in non-atopic, atopic and strongly atopic patients with blood eosinophil counts ≥ 300 cells/μL; consistent improvements in ACQ-5 were not observed in patients with blood eosinophil counts < 150 or ≥ 150– 300 cells/μL. Reductions in clinically significant exacerbations with mepolizumab versus placebo were also observed irrespective of sensitivity to HDMs.Conclusion: Mepolizumab was associated with a trend for reductions in clinically significant exacerbations and improved asthma control versus placebo in patients with severe eosinophilic asthma, irrespective of atopic status or HDM sensitivity.Keywords: allergens and epitopes, eosinophils, asthma, asthma treatments, biologics
