Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia
Michel Laviolette,David Gossage,Gail M. Gauvreau,Richard Leigh,Ron Olivenstein,Rohit K. Katial,William W. Busse,Sally E. Wenzel,Yanping Wu,Vivekananda Datta,Roland Kolbeck,Nestor A. Molfino +11 more
Reads0
Chats0
TLDR
Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosInophils counts in bone marrow and peripheral blood and the safety profile supports further development.Abstract:
Background Many asthmatic patients exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor α, inducing apoptosis through antibody-dependent cell-mediated cytotoxicity. Objectives We sought to evaluate the safety of benralizumab in adults with eosinophilic asthma and its effects on eosinophil counts in airway mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood. Methods In this multicenter, double-blind, placebo-controlled phase I study, 13 subjects were randomized to single-dose intravenous placebo or 1 mg/kg benralizumab (day 0; cohort 1), and 14 subjects were randomized to 3 monthly subcutaneous doses of placebo or 100 or 200 mg of benralizumab (days 0, 28, and 56; cohort 2). Cohorts 1 and 2 were consecutive. Results The incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. In cohort 1 intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophil counts (day 28; placebo: +19.6%; P = .28), as well as an 18.7% decrease (day 21) in sputum and a 100% decrease (day 28) in blood counts. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n = 4). In cohort 2 subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophil counts (day 84; placebo, 46.7%; P = .06), as well as an 89.9% decrease (day 28) in sputum and a 100% decrease (day 84) in blood counts. Conclusion Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosinophil counts in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess the clinical benefit in asthmatic patients.read more
Citations
More filters
Journal ArticleDOI
Emerging Biological Therapies in Severe Eosinophilic Asthma
TL;DR: The need for more phenotype-directed therapies in severe asthma is outlined, and the supporting evidence for monoclonal antibodies directed against key pro-eosinophilic T-helper 2 (Th2) inflammatory cytokines as additive agents in the treatment of severe asthma with an eosInophilic phenotype is discussed.
Journal ArticleDOI
Siglec-8 on murine eosinophils: A new model for an old target.
TL;DR: The protein sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8) is a potential therapeutic target for allergic disorders as it is expressed on the surface of human eosinophil, basophils, and mast cells and engages in apoptosis.
Journal ArticleDOI
[Benralizumab: Targeting the IL-5 Receptor in Severe Eosinophilic Asthma].
Jörg D. Leuppi,Peter Schmid-Grendelmeier,Thomas Rothe,Christophe von Garnier,Hans-Uwe Simon,Claudio Schuoler,Gunther Pendl,Markus Solèr +7 more
TL;DR: Benralizumab as discussed by the authors targets the IL-5 Receptor in severe Eosinophilic Asthma using specific monoclonal antibodies with few side effects, and shows promising results for selected severe asthmatics.
Journal ArticleDOI
Benralizumab: eficacia y seguridad en pacientes con asma grave eosinofílica.
Genny Chaia,Ubaldo J. Martin,Arturo Cortés-Telles,Fernando Morett,José Julio Gutiérrez-Mujica,Adriana Zepeda-Gómez,Alberto Hegewisch,Rogelio Ramses Hernández +7 more
TL;DR: Benralizumab is a humanized monoclonal antibody, which joins with high affinity and specificity to the alpha subunit of the IL-5 receptor on the surface of eosinophils and other cells, which leads to a direct, rapid and nearly complete depletion in both peripheral blood and bone marrow.
Book ChapterDOI
Pharmacologic Therapies for Severe Asthma
TL;DR: Recent advances in pharmacologic treatment of severe asthma will be introduced including improved current medications, potent nonspecific anti-inflammatory agents, endotype-targeted treatments, specific treatment for comorbidities, and potential therapeutic candidates.
References
More filters
Journal ArticleDOI
Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.
Ian D. Pavord,Stephanie Korn,Peter H. Howarth,Eugene R. Bleecker,Roland Buhl,Oliver N. Keene,Hector Ortega,Pascal Chanez +7 more
TL;DR: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.
Journal ArticleDOI
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma
Pranabashis Haldar,Christopher E. Brightling,Beverley Hargadon,Sunil Gupta,W Monteiro,Ana R. Sousa,Richard P. Marshall,Peter Bradding,Ruth H. Green,Andrew J. Wardlaw,Ian D. Pavord +10 more
TL;DR: The results of this study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population.
Journal ArticleDOI
Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.
Ruth H. Green,Christopher E. Brightling,S McKenna,Beverley Hargadon,Debbie Parker,Peter Bradding,Andrew J. Wardlaw,Ian D. Pavord +7 more
TL;DR: A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.
Journal ArticleDOI
Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia
Parameswaran Nair,Marcia Margaret Menezes Pizzichini,Melanie Kjarsgaard,Mark D. Inman,Ann Efthimiadis,Emilio Pizzichini,Frederick E. Hargreave,Paul M. O'Byrne +7 more
TL;DR: Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with spUTum eOSinophilia despiteprednisone treatment.