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https://www.readbyqxmd.com/read/29049762/in-severe-asthma-benralizumab-reduced-daily-oral-glucocorticoid-dose-and-asthma-exacerbations-at-6-months
#1
Diego J Maselli, Jay I Peters
No abstract text is available yet for this article.
October 17, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#2
Jason Gotlib
DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29017221/-biologicals-in-the-treatment-of-bronchial-asthma
#3
I Haasler, C Taube
Biologicals are a therapeutic option for patients with severe asthma. Difficult asthma in patients with untreated comorbidities or persistent trigger factors is much more common than severe refractory asthma. Optimized medical treatment, adherence to medication, elimination of trigger factors and treatment of comorbidities are essential before escalating the therapy with a biological. A careful phenotyping of patient with severe asthma is necessary because all available biological are only effective in certain phenotypes of the disease...
October 2017: Pneumologie
https://www.readbyqxmd.com/read/28971769/new-therapeutic-targets-and-drugs-for-the-treatment-of-asthma
#4
Mateus Feitosa Alves, Diogo Vilar da Fonsec, Sílvia Adelaide Linhares de Melo, Marcus Tullius Scotti, Luciana Scotti, Sócrates Golzio Dos Santos, Margareth de Fátima Formiga Melo Diniz
Asthma is an inflammatory disease which affects millions of people worldwide. Therefore, it is necessary search for new sources of therapies for the treatment of these patients in order to improve their quality of life. From content analysis of new therapeutic targets literature, there are various targets and drugs reported as promising for treatment asthma. Interleukins involved in inflammatory processes are often presented as candidate targets for new drugs. The action of such therapeutics would not only affect interleukins, but also in their receptors...
September 27, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28948572/overlapping-effects-of-new-monoclonal-antibodies-for-severe-asthma
#5
REVIEW
Christian Domingo
Among the monoclonal antibodies (mAbs) developed for severe asthma treatment, three have already been marketed. Omalizumab was the first, more than 10 years ago; today, mepolizumab and reslizumab are also available in the European Union and the US. Omalizumab blocks free immunoglobulin E (IgE), mepolizumab and reslizumab block an interleukin (IL-5). In the near future, dupilumab and benralizumab are expected to emerge as two new alternatives. Benralizumab blocks the receptor for IL-5 (IL5-Rα) and has a direct cytotoxic effect on eosinophils, and dupilumab blocks the α-unit of the heterodimeric receptor for IL-4 and IL-13 (IL-4Rα); as a result, dupilumab can block both IL-4 and IL-13...
September 25, 2017: Drugs
https://www.readbyqxmd.com/read/28933516/anti-il5-therapies-for-asthma
#6
REVIEW
Hugo A Farne, Amanda Wilson, Colin Powell, Lynne Bax, Stephen J Milan
BACKGROUND: This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the activation of eosinophils, which cause airway inflammation and are a classic feature of asthma. Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function...
September 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28930508/glucocorticoid-sparing-of-benralizumab-in-asthma
#7
LETTER
Chao Cao, Xue Kong, Xiaoping Huang
New England Journal of Medicine, Volume 377, Issue 12, Page 1204-1205, September 2017.
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28930507/glucocorticoid-sparing-of-benralizumab-in-asthma
#8
LETTER
Parameswaran Nair, Peter Barker, Mitchell Goldman
No abstract text is available yet for this article.
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#9
REVIEW
Francesco Menzella, Carla Galeone, Francesca Bertolini, Claudia Castagnetti, Nicola Facciolongo
The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28919200/predictors-of-enhanced-response-with-benralizumab-for-patients-with-severe-asthma-pooled-analysis-of-the-sirocco-and-calima-studies
#10
J Mark FitzGerald, Eugene R Bleecker, Andrew Menzies-Gow, James G Zangrilli, Ian Hirsch, Paul Metcalfe, Paul Newbold, Mitchell Goldman
BACKGROUND: Benralizumab is an anti-eosinophilic, anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe, uncontrolled asthma. We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories. METHODS: This study is a pooled analysis of the results from the randomised, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase 3 studies...
September 8, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28737051/pharmacokinetic-pharmacodynamic-drug-evaluation-of-benralizumab-for-the-treatment-of-asthma
#11
REVIEW
Maria Gabriella Matera, Luigino Calzetta, Barbara Rinaldi, Mario Cazzola
In many severe asthmatics, eosinophils cause inflammation and airways hyperresponsiveness, resulting in frequent exacerbations, impaired lung function, and reduced quality of life. Interleukin-5 (IL-5) is a key cytokine for eosinophil growth, differentiation, recruitment, activation, and survival. Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the α subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28724278/reductions-in-eosinophil-biomarkers-by-benralizumab-in-patients-with-asthma
#12
COMMENT
Mirhojjat Khorasanizadeh, Mahsa Eskian, Nima Rezaei
No abstract text is available yet for this article.
May 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28644104/the-association-between-blood-eosinophil-count-and-benralizumab-efficacy-for-patients-with-severe-uncontrolled-asthma-subanalyses-of-the-phase-iii-sirocco-and-calima-studies
#13
Mitchell Goldman, Ian Hirsch, James G Zangrilli, Paul Newbold, Xiao Xu
OBJECTIVE: Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β2-agonists (ICS/LABA), significantly reduced asthma exacerbations, improved lung function, and reduced symptoms for patients with severe, uncontrolled asthma with blood eosinophil counts ≥300 cells/μL in the Phase III SIROCCO and CALIMA studies. To understand the efficacy and safety of benralizumab for patients with eosinophil-driven disease with blood eosinophil counts lower than 300 cells/μL, we evaluated the effect of applying an eosinophil cutoff of ≥150 cells/μL...
July 19, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28583618/new-anti-eosinophil-drugs-for-asthma-and%C3%A2-copd-targeting-the-trait
#14
REVIEW
Elisabeth H Bel, Anneke Ten Brinke
Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait...
June 2, 2017: Chest
https://www.readbyqxmd.com/read/28545978/benralizumab-for-patients-with-mild-to-moderate-persistent-asthma-bise-a-randomised-double-blind-placebo-controlled-phase-3-trial
#15
Gary T Ferguson, J Mark FitzGerald, Eugene R Bleecker, Michel Laviolette, David Bernstein, Craig LaForce, Lyndon Mansfield, Peter Barker, Yanping Wu, Maria Jison, Mitchell Goldman
BACKGROUND: Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18-75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV1) of at least 12% at screening, from 52 clinical research centres in six countries...
July 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28530840/oral-glucocorticoid-sparing-effect-of-benralizumab-in-severe-asthma
#16
RANDOMIZED CONTROLLED TRIAL
Parameswaran Nair, Sally Wenzel, Klaus F Rabe, Arnaud Bourdin, Njira L Lugogo, Piotr Kuna, Peter Barker, Stephanie Sproule, Sandhia Ponnarambil, Mitchell Goldman
BACKGROUND: Many patients with severe asthma rely on oral glucocorticoids to manage their disease. We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia. METHODS: In a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28502824/human-group-2-innate-lymphoid-cells-do-not-express-the-il-5-receptor
#17
Adam K A Wright, Cathryn Weston, Batika M J Rana, Christopher E Brightling, David J Cousins
Group 2 innate lymphoid cells (ILC2s) are upstream regulators of IL-5-dependent eosinophil function in asthma. We've shown that ILC2s do not express the IL-5R and thus IL-5R-dependent therapeutic interventions (e.g. Benralizumab) are unlikely to be mediated directly on ILC2s.
May 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28406319/benralizumab-as-a-potential-treatment-of-asthma
#18
Sabina Antonela Antoniu
Current anti-inflammatory asthma therapies including inhaled corticosteroids and leukotriene modifiers, are not always able to appropriately control the disease and other approaches are needed. These therapies specific target IgE (omalizumab) or IL-5 (mepolizumab). However, there is research underway investigating interleukin-based monoclonal antibodies such as benralizumab, an anti-IL-5R monoclonal antibody which is currently in phase III clinical development. Areas covered: This review summarizes the existing preclinical and clinical data of benralizumab...
July 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28379047/benralizumab-for-the-treatment-of-asthma
#19
Tara Vinyette Saco, Amber N Pepper, Richard F Lockey
The classification of asthma into phenotypes and endotoypes allows for the use of targeted therapies, including three biologics which target interleukin 5 (IL-5) signaling in eosinophilic asthma. Areas covered: As of December 2016, two monoclonal antibodies, mepolizumab and reslizumab, are approved by U.S. Food and Drug Administration and one, benralizumab, is in clinical development. Two phase 3 trials for benralizumab, SIROCCO and CALIMA, were published in September 2016. Although there are no direct comparisons among these three anti-IL-5 therapies, the goal of this review is to summarize the current data and discuss their potential similarities and differences, with a focus on benralizumab...
April 19, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28109128/population-pharmacokinetics-and-pharmacodynamics-of-benralizumab-in-healthy-volunteers-and-patients-with-asthma
#20
B Wang, L Yan, Z Yao, L K Roskos
Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG) 1 κ monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N = 48) and four studies in patients with asthma (N = 152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the central compartment and first-order absorption from the subcutaneous dosing site...
April 2017: CPT: Pharmacometrics & Systems Pharmacology
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