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https://www.readbyqxmd.com/read/29133975/severe-eosinophilic-asthma-from-the-pathogenic-role-of-interleukin-5-to-the-therapeutic-action-of-mepolizumab
#1
REVIEW
Corrado Pelaia, Alessandro Vatrella, Maria Teresa Busceti, Luca Gallelli, Rosa Terracciano, Rocco Savino, Girolamo Pelaia
Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that has been recently approved as an add-on biological treatment for severe eosinophilic asthma, by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, mepolizumab is also currently included within the step 5 of the Global Initiative for Asthma guidelines, as an add-on therapy for severe uncontrolled asthma. The relevant therapeutic benefits detectable in patients with refractory eosinophilic asthma receiving mepolizumab depend on the pivotal pathogenic role played by IL-5 in these subjects...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29133221/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-syndrome-successfully-treated-with-mepolizumab
#2
Nikhita Ange, Sonia Alley, Suran L Fernando, Luke Coyle, James Yun
No abstract text is available yet for this article.
November 10, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29118815/response-to-case-report-airway-autoimmune-responses-in-severe-eosinophilic-asthma-following-low-dose-mepolizumab-therapy
#3
I J Pouliquen, P Howarth, D Austin, G Gunn, E Meyer, R G Price, E Bradford
No abstract text is available yet for this article.
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/29108767/biologics-in-the-treatment-of-severe-asthma
#4
REVIEW
S Quirce, E Phillips-Angles, J Domínguez-Ortega, P Barranco
Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids and with a second controller drug to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy. Patients with uncontrolled severe asthma require additional treatment options as add-on therapy, including biologics. Biologic therapies in asthma are designed to block key immune regulators, such as IgE, or certain pro-inflammatory cytokines, e.g. interleukin (IL)-5, IL-4, IL-13 or IL-17...
November 3, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29059618/development-of-a-robust-reporter-gene-based-assay-for-the-bioactivity-determination-of-il-5-targeted-therapeutic-antibodies
#5
Zhihao Fu, Chuanfei Yu, Lan Wang, Kai Gao, Gangling Xu, Wenbo Wang, Junxia Cao, Junzhi Wang
Eosinophilic asthma is characterized by the eosinophilic inflammation with the allergen independent activation of Th2 lymphocytes. Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5Rα have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab. Accurate determination of bioactivity is crucial for the safety and efficacy of therapeutic antibodies. The current mode of action (MOA) based method used in the quality control and stability tests for anti-IL-5 mAbs is anti-proliferation assay, which is tedious with long duration and high variation...
September 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#6
REVIEW
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/29036018/precision-medicine-in-asthma-linking-phenotypes-to-targeted-treatments
#7
Kian F Chung
PURPOSE OF REVIEW: Asthma is a heterogeneous disease consisting of different phenotypes that are driven by different mechanistic pathways. The purpose of this review is to emphasize the important role of precision medicine in asthma management. RECENT FINDINGS: Despite asthma heterogeneity, the approach to management has been on the basis of disease severity, with the most severe patients reserved for the maximum treatments with corticosteroids and bronchodilators...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29033420/usefulness-of-bronchial-thermoplasty-for-patients-with-a-deteriorating-lung-function-a-report-of-two-cases
#8
Daisuke Minami, Chihiro Ando, Takamasa Nakasuka, Yoshitaka Iwamoto, Ken Sato, Keiichi Fujiwara, Takuo Shibayama, Toshirou Yonei, Toshio Sato
Bronchial thermoplasty is a novel procedure for patients with severe asthma showing a stable lung function. We herein report two cases with a deteriorating lung function. The lung function tended to improve in one case, while the other case discontinued mepolizumab medication after the procedure. Treatment was performed safely under general anesthesia in both cases. The use of bronchial thermoplasty may therefore be useful for the treatment of patients with a deteriorating lung function.
October 16, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29017221/-biologicals-in-the-treatment-of-bronchial-asthma
#9
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/28986919/mepolizumab-a-novel-option-for-the-treatment-of-hypereosinophilic-syndrome-in-childhood
#10
Carsten Schwarz, Thilo Müller, Susanne Lau, Kirn Parasher, Doris Staab, Ulrich Wahn
BACKGROUND: Mepolizumab was originally intended as a therapeutic agent for atopic asthma in adults, and consequently little is known about its use in children. Up to now corticosteroids have formed the basis of the initial treatment of hypereosinophilic syndromes and are shown to be effective in most patients. To analyse the effect of mepolizumab in children is the aim of this study. METHODS: We are reporting the experience of the effect of mepolizumab in two paediatric patients of hypereosinophilic syndrome that was not sufficiently controlled by other drugs...
October 6, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28948572/overlapping-effects-of-new-monoclonal-antibodies-for-severe-asthma
#11
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...
October 2017: Drugs
https://www.readbyqxmd.com/read/28933516/anti-il5-therapies-for-asthma
#12
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/28933002/mepolizumab-for-treating-severe-eosinophilic-asthma-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#13
REVIEW
Iñigo Bermejo, Matt Stevenson, Katy Cooper, Sue Harnan, Jean Hamilton, Mark Clowes, Christopher Carroll, Tim Harrison, Shironjit Saha
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company (GlaxoSmithKline) that manufactures mepolizumab (Nucala(®)) to submit evidence on the clinical and cost effectiveness of mepolizumab for the treatment of severe eosinophilic asthma. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent evidence review group (ERG). The ERG produced a review of the evidence for the clinical and cost effectiveness of mepolizumab as add-on to standard of care (SoC) compared with SoC and omalizumab, based upon the company's submission to NICE...
September 20, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28926280/mepolizumab-attenuates-airway-eosinophil-numbers-but-not-their-functional-phenotype-in-asthma
#14
Gail M Gauvreau, Roma Sehmi
No abstract text is available yet for this article.
September 19, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#15
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/28918644/anti-ige-and-anti-il5-biologic-therapy-in-the-treatment-of-nasal-polyposis-a-systematic-review-and-meta-analysis
#16
REVIEW
Alexander Rivero, Jonathan Liang
OBJECTIVE: To determine the role of biologic therapy on sinonasal symptoms and objective outcomes in chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: PubMed, OVID MEDLINE, and Cochrane Central were reviewed from 2000 to 2015. Inclusion criteria included English-language studies containing original data on biologic therapy in CRSwNP patients with reported outcome measures. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools...
November 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28915080/weight-adjusted-intravenous-reslizumab-in-severe-asthma-with-inadequate-response-to-fixed-dose-subcutaneous-mepolizumab
#17
Manali Mukherjee, Fernando Aleman Paramo, Melanie Kjarsgaard, Brittany Salter, Gayatri Nair, Nicola LaVigne, Katherine Radford, Roma Sehmi, Parameswaran Nair
BACKGROUND: Clinical benefits of fixed-dose 100 mg subcutaneous (SC) mepolizumab in prednisone-dependent patients are modest when sputum eosinophilia is not adequately controlled. This study compared treatment response of weight-adjusted intravenous (IV) Reslizumab in patients previously treated with 100 mg SC Mepolizumab. METHOD: 10 prednisone-dependent asthmatics (sputum eosinophils >3% and blood eosinophils > 300cells/μL), who had previously received Mepolizumab (100 mg SC Q4W) for at least 1 year, received two infusions of placebo (Q4W) followed by 4 infusions of 3...
September 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28910970/antibody-therapy-for-the-management-of-severe-asthma-with-eosinophilic-inflammation
#18
Ken Ohta, Hiroyuki Nagase, Maho Suzukawa, Shin Ohta
One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28893134/mepolizumab-for-eosinophilic-chronic-obstructive-pulmonary-disease
#19
RANDOMIZED CONTROLLED TRIAL
Ian D Pavord, Pascal Chanez, Gerard J Criner, Huib A M Kerstjens, Stephanie Korn, Njira Lugogo, Jean-Benoit Martinot, Hironori Sagara, Frank C Albers, Eric S Bradford, Stephanie S Harris, Bhabita Mayer, David B Rubin, Steven W Yancey, Frank C Sciurba
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5. METHODS: We performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy...
October 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28862877/mepolizumab-attenuates-airway-eosinophil-numbers-but-not-their-functional-phenotype-in-asthma
#20
Elizabeth A Kelly, Stephane Esnault, Lin Ying Liu, Michael D Evans, Mats W Johansson, Sameer Mathur, Deane F Mosher, Loren C Denlinger, Nizar N Jarjour
RATIONALE: Mepolizumab, an interleukin-5 blocking antibody, reduces exacerbations in severe eosinophilic asthma patients. Mepolizumab arrests eosinophil maturation; however, the functional phenotype of eosinophils that persist in the blood and airway after administration of interleukin-5 neutralizing antibodies has not been reported. OBJECTIVE: To determine the effect of anti-IL-5 antibody on the numbers and phenotypes of allergen-induced circulating and airway eosinophils...
September 1, 2017: American Journal of Respiratory and Critical Care Medicine
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