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https://www.readbyqxmd.com/read/27906698/ige-and-eosinophils-as-therapeutic-targets-in-asthma
#1
Tanvi R Patel, Sanjiv Sur
PURPOSE OF REVIEW: Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27889561/inhibition-of-interleukin-5-induced-false-positive-anti-drug-antibody-responses-against-mepolizumab-through-the-use-of-a-competitive-blocking-antibody
#2
Karen Liao, Erik Meyer, Thomas N Lee, Amy Loercher, Daniel Sikkema
Mepolizumab, a humanized IgG1 monoclonal antibody that blocks native homodimeric interleukin-5 (IL-5) from binding to the IL-5 receptor, has recently been approved for treatment of severe eosinophilic asthma. Our initial immunogenicity assay method for phase I and II studies utilized a bridging electrochemiluminescence format with biotin and ruthenium-labelled mepolizumab linked by anti-drug antibodies (ADA). We discovered that IL-5 significantly increased in dosed subjects from a phase II study and that the increased IL-5 was in the form of a drug-bound complex...
November 23, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27885827/a-mathematical-modeling-approach-to-understanding-the-effect-of-anti-interleukin-therapy-on-eosinophils
#3
T Karelina, V Voronova, O Demin, G Colice, B M Agoram
Emerging T-helper type 2 (Th2 ) cytokine-based asthma therapies, such as tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL-5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways...
November 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27859832/comparison-of-anti-interleukin-5-therapies-in-patients-with-severe-asthma-global-and-indirect-meta-analyses-of-randomized-placebo-controlled-trials
#4
Yann Cabon, Nicolas Molinari, Gregory Marin, Isabelle Vachier, Anne Sophie Gamez, Pascal Chanez, Arnaud Bourdin
BACKGROUND: Inconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. METHODS: We identified all RCTs with anti-IL5 treatments for asthma patients over the 1990-September 2015 period. RCT were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were: exacerbation rate reduction, FEV1 changes, ACQ-5 improvement, adverse events and serious adverse events...
November 10, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27856823/mepolizumab-in-the-management-of-severe-eosinophilic-asthma-in-adults-current-evidence-and-practical-experience
#5
REVIEW
Gilda Varricchi, Diego Bagnasco, Matteo Ferrando, Francesca Puggioni, Giovanni Passalacqua, Giorgio W Canonica
Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF...
November 17, 2016: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/27834175/severe-asthma-anti-ige-or-anti-il-5
#6
REVIEW
Evgenia Papathanassiou, Stelios Loukides, Petros Bakakos
Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator...
2016: European Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27803792/mepolizumab-for-severe-refractory-eosinophilic-asthma-evidence-to-date-and-clinical-potential
#7
REVIEW
Francesco Menzella, Mirco Lusuardi, Carla Galeone, Sofia Taddei, Nicola Facciolongo, Luigi Zucchi
Severe asthma is characterized by major impairment of quality of life, poor symptom control and frequent exacerbations. Inflammatory, clinical and causative factors identify different phenotypes and endotypes of asthma. In the last few years, new treatment options have allowed for targeted treatments according to the different phenotypes of the disease. To accurately select a specific treatment for each asthmatic variant, the identification of appropriate biomarkers is required. Eosinophilic asthma is a distinct phenotype characterized by thickening of the basement membrane and corticosteroid responsiveness...
November 2016: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/27796795/interleukin-5-antagonists-usher-in-a-new-generation-of-asthma-therapy
#8
REVIEW
Matthew P Giannetti, Juan C Cardet
Asthma is the most common chronic respiratory disease in the USA. A subset of patients with asthma have refractory symptoms, persistent eosinophilic inflammation, and recurrent exacerbations despite maximal medical therapy. The monoclonal antibodies targeting the IL-5 pathway are a new class of medications designed to target severe eosinophilic asthma. There are two medications clinically available: mepolizumab and reslizumab, both of which target IL-5. A third medication, benralizumab, is currently under development and targets the IL-5 receptor...
November 2016: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/27773786/monoclonal-antibody-therapy-for-the-treatment-of-asthma-and-chronic-obstructive-pulmonary-disease-with-eosinophilic-inflammation
#9
John Nixon, Paul Newbold, Tomas Mustelin, Gary P Anderson, Roland Kolbeck
Eosinophils have been linked with asthma for more than a century, but their role has been unclear. This review discusses the roles of eosinophils in asthma and chronic obstructive pulmonary disease (COPD) and describes therapeutic antibodies that affect eosinophilia. The aims of pharmacologic treatments for pulmonary conditions are to reduce symptoms, slow decline or improve lung function, and reduce the frequency and severity of exacerbations. Inhaled corticosteroids (ICS) are important in managing symptoms and exacerbations in asthma and COPD...
October 20, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27757000/mepolizumab-nucala-for-severe-eosinophilic-asthma
#10
Min Sung Choy, Deepali Dixit, Mary Barna Bridgeman
Mepolizumab (Nucala) for severe eosinophilic asthma.
October 2016: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/27726946/meta-analysis-of-asthma-related-hospitalization-in-mepolizumab-studies-of-severe-eosinophilic-asthma
#11
Steven W Yancey, Hector G Ortega, Oliver N Keene, Bhabita Mayer, Necdet B Gunsoy, Christopher E Brightling, Eugene R Bleecker, Pranabashis Haldar, Ian D Pavord
BACKGROUND: Studies show that mepolizumab can reduce the frequency of clinically significant exacerbations in patients with severe eosinophilic asthma, compared with placebo. However, important events such as hospitalizations and emergency room visits are rare and difficult to characterize in single studies. OBJECTIVE: We sought to compare hospitalization or hospitalization and/or emergency room visit rates in patients with severe eosinophilic asthma treated with mepolizumab or placebo in addition to standard of care for at least 24 weeks...
October 4, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27697814/european-drug-market-entries-2015-with-new-mechanisms-of-action
#12
Titus W P van den Heuvel, Adam F Cohen, Robert Rissmann
In this article, we consider the new drugs approved for the European market in 2015. We present a summary of the new mechanisms of action introduced and highlight three new mechanisms of action with a potentially high future impact: PCSK9 inhibition (alirocumab (Praluent®) and evolocumab (Repatha®)) for hypercholesterolaemia, neprilysin inhibition (sacubitril in combination with valsartan (Entresto®)) for heart failure, and interleukin-5 inhibition (mepolizumab (Nucala®)) for asthma.
October 2016: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/27668056/nucala-mepolizumab-first-il-5-antagonist-monoclonal-antibody-fda-approved-for-maintenance-treatment-of-patients-with-severe-asthma
#13
Loretta Fala
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
https://www.readbyqxmd.com/read/27613653/novel-biologicals-for-the-treatment-of-allergic-diseases-and-asthma
#14
REVIEW
Hern-Tze Tina Tan, Kazunari Sugita, Cezmi A Akdis
PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP)...
October 2016: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/27612492/the-clinical-profile-of-benralizumab-in-the-management-of-severe-eosinophilic-asthma
#15
Francesco Menzella, Mirco Lusuardi, Carla Galeone, Nicola Facciolongo, Luigi Zucchi
Despite several therapeutic choices, 10-20% of patients with severe uncontrolled asthma do not respond to maximal best standard treatments, leading to a healthcare expenditure of up to 80% of overall costs for asthma. Today, there are new important therapeutic strategies, both pharmacological and interventional, that can result in improvement of severe asthma management, such as omalizumab, bronchial thermoplasty and other biological drugs, for example, mepolizumab, reslizumab and benralizumab. The availability of these new treatments and the increasing knowledge of the different asthmatic phenotypes and endotypes makes correct patient selection increasingly complex and important...
September 9, 2016: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/27553751/long-term-efficacy-and-safety-of-mepolizumab-in-patients-with-severe-eosinophilic-asthma-a-multi-center-open-label-phase-iiib-study
#16
Njira Lugogo, Christian Domingo, Pascal Chanez, Richard Leigh, Martyn J Gilson, Robert G Price, Steven W Yancey, Hector G Ortega
PURPOSE: Patients with severe eosinophilic asthma often experience recurrent asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), treatment with intravenous or subcutaneous mepolizumab was associated with significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) requirements compared with placebo. The purpose of this study was to assess the long-term safety and efficacy of subcutaneous mepolizumab treatment in patients with severe eosinophilic asthma...
September 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27519953/eosinophil-peroxidase-activates-cells-by-her2-receptor-engagement-and-%C3%AE-1-integrin-clustering-with-downstream-mapk-cell-signaling
#17
Kerrie Hennigan, Paul J Conroy, Marie-Therese Walsh, Mohamed Amin, Richard O'Kennedy, Patmapriya Ramasamy, Gerald J Gleich, Zeshan Siddiqui, Senan Glynn, Olive McCabe, Catherine Mooney, Brian J Harvey, Richard W Costello, Jean McBryan
Eosinophils account for 1-3% of peripheral blood leukocytes and accumulate at sites of allergic inflammation, where they play a pathogenic role. Studies have shown that treatment with mepolizumab (an anti-IL-5 monoclonal antibody) is beneficial to patients with severe eosinophilic asthma, however, the mechanism of precisely how eosinophils mediate these pathogenic effects is uncertain. Eosinophils contain several cationic granule proteins, including Eosinophil Peroxidase (EPO). The main significance of this work is the discovery of EPO as a novel ligand for the HER2 receptor...
October 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27497278/advances-in-asthma-2015-across-the-lifespan
#18
Andrew H Liu, William C Anderson, Cullen M Dutmer, Daniel A Searing, Stanley J Szefler
In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened...
August 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27453494/molecularly-targeted-therapies-for-asthma-current-development-challenges-and-potential-clinical-translation
#19
REVIEW
Ibrahim Sulaiman, Jonathan Chee Woei Lim, Hon Liong Soo, Johnson Stanslas
Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs...
October 2016: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27378934/the-therapeutic-potential-of-targeting-cytokine-alarmins-to-treat-allergic-airway-inflammation
#20
REVIEW
Chandler B Sy, Mark C Siracusa
Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects...
2016: Frontiers in Physiology
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