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Katherine L Tuttle, Kathleen M Buchheit, Tanya M Laidlaw, Katherine N Cahill
No abstract text is available yet for this article.
February 28, 2018: Journal of Allergy and Clinical Immunology in Practice
Mathew X Joseph, Lauren E Jenkins, Michael E Wechsler, Loretta S Davis
No abstract text is available yet for this article.
February 21, 2018: JAMA Dermatology
Kevin L Winthrop, Xavier Mariette, Jose T Silva, Esther Benamu, Leonard H Calabrese, Alexandre Dumusc, Josef S Smolen, José María Aguado, Mario Fernández-Ruiz
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
Hector Ortega, Steven W Yancey, Oliver N Keene, Necdet B Gunsoy, Frank C Albers, Peter H Howarth
BACKGROUND: Limited data describe the association between the frequency of asthma exacerbations and the decline in lung function in severe asthma. OBJECTIVE: To determine whether asthma exacerbations are associated with enhanced decline in lung function. METHODS: Changes in lung function were analyzed retrospectively using data from the DREAM and MENSA studies of mepolizumab intervention in patients with severe asthma. Patients were either nonsmokers or former smokers...
February 1, 2018: Journal of Allergy and Clinical Immunology in Practice
N Tsetsos, J K Goudakos, D Daskalakis, I Konstantinidis, K Markou
BACKGROUND: Monoclonal antibodies have been proposed as a novel therapy in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this systematic review was to evaluate their efficacy and safety. METHODOLOGY: A literature search was performed in MEDLINE, Web of Science, the Cochrane Library and multiple trial registries followed by extensive hand-searching for the identification of relevant studies. Only randomized controlled trials (RCTs) comparing the use of monoclonal antibodies with placebo or another therapy in adult patients with CRSwNP were included...
February 3, 2018: Rhinology
Emily Ko, Mirna Chehade
Eosinophilic esophagitis (EoE) is an immune-mediated, chronic esophageal disease characterized by esophageal symptoms and esophageal eosinophilia. It is triggered by foods and possibly by environmental allergens. Currently, there are no FDA-approved therapies for EoE. Commonly used treatments include dietary restrictions and topical corticosteroids. Many of these therapies are suboptimal in their efficacy, have side effects, or diminish patients' quality of life. Biologic therapies for EoE have therefore been sought as an alternative...
January 25, 2018: Clinical Reviews in Allergy & Immunology
Maciej Kupczyk, Piotr Kuna
IL-5 is a key cytokine responsible for the maturation, recruitment and survival of eosinophils. The role of eosinophils in pathomechanisms of severe asthma and association of those cells with frequent exacerbations are well accepted. Novel biologic agents including anti-IL-5 antibodies (mepolizumab and reslizumab) as well as anti-IL-5 receptor α chain (benralizumab) have been developed. Benralizumab (Fasenra™) leads to reduced eosinophil counts in airway mucosa, blood, sputum and a clear inhibition of eosinophil differentiation and maturation in the bone marrow...
April 2018: Immunotherapy
Necdet B Gunsoy, Sarah M Cockle, Steven W Yancey, Oliver N Keene, Eric S Bradford, Frank C Albers, Ian D Pavord
BACKGROUND: Mepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. The early identification of patients likely to receive long-term benefit from treatment could ensure effective resource allocation. OBJECTIVE: To assess potential continuation rules for mepolizumab in addition to initiation criteria defined as 2 or more exacerbations in the previous year and blood eosinophil counts of 150 cells/μL or more at initiation or 300 cells/μL or more in the previous year...
December 16, 2017: Journal of Allergy and Clinical Immunology in Practice
Massimo Caruso, Jaymin Morjaria, Rosalia Emma, Maria Domenica Amaradio, Riccardo Polosa
Asthma is a chronic inflammatory multifactorial disorder of the airways characterized by the involvement of immune cells and mediators in its onset and maintenance. Traditional therapeutic strategies have been unsatisfactory in controlling the underlying pathology, especially in the more severe states. Hence in the last couple of decades, new biological approaches targeting molecular mediators have been developed. In this narrative review we examine biological agents currently available for the management of severe asthma, focusing our attention on their clinical application, pros and cons, and in particular on gaps regarding the use of these agents...
March 2018: Internal and Emergency Medicine
Mahsa Eskian, MirHojjat Khorasanizadeh, Amal H Assa'ad, Nima Rezaei
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus affecting both children and adults, with debilitating and progressive symptoms. EoE has shown an explosive epidemiological rise in the past few decades. Many patients experience a poor level of disease control despite maximal use of available guideline-based therapies, which seriously hampers their quality of life. Diet restrictions and systemic and topical corticosteroids are the current mainstays of EoE therapy, but are associated with significant efficacy, treatment compliance, and safety issues such as oral or esophageal candidiasis, growth retardation, osteopenia, osteoporosis, glucose intolerance, and cataract formation...
December 12, 2017: Clinical Reviews in Allergy & Immunology
Lynn Condreay, Mathias Chiano, Hector Ortega, Natalie Buchan, Elizabeth Harris, Eugene R Bleecker, Philip J Thompson, Marc Humbert, Peter Gibson, Steven Yancey, Soumitra Ghosh
BACKGROUND AND OBJECTIVES: Treatment with mepolizumab, a humanized monoclonal antibody to interleukin-5, reduces the rate of asthma exacerbations and the requirement for systemic glucocorticoids while maintaining asthma control. Treatment decisions are guided by predictors of response, including blood eosinophil thresholds in patients with frequent exacerbations despite intensive anti-inflammatory and controller treatment. Identification of additional predictors of response could aid treatment decisions...
November 2017: Respiratory Medicine
Steven W Yancey, Oliver N Keene, Frank C Albers, Hector Ortega, Stewart Bates, Eugene R Bleecker, Ian Pavord
The last decade has seen the approval of several new biologics for the treatment of severe asthma-targeting specific endotypes and phenotypes. This review will examine how evidence generated from the mepolizumab clinical development program showed that blood eosinophil counts, rather than sputum or tissue eosinophil counts, evolved as a pharmacodynamic and predictive biomarker for the efficacy of treatment with mepolizumab in patients with severe eosinophilic asthma. Based on the available evidence and combined with clinical judgement, a baseline blood eosinophil threshold of 150 cells/μL or greater or a historical blood eosinophil threshold of 300 cells/μL or greater will allow selection of patients with severe eosinophilic asthma who are most likely to achieve clinically significant reductions in the rate of exacerbations with mepolizumab treatment...
December 2017: Journal of Allergy and Clinical Immunology
Francesco Menzella, Carla Galeone, Mirco Lusuardi, Anna Simonazzi, Claudia Castagnetti, Patrizia Ruggiero, Nicola Facciolongo
Severe asthma affects between 5% and 10% of patients with asthma worldwide and requires best standard therapies at maximal doses, but there is a subgroup of patients refractory to all treatments. We share a case report of a 53-year-old woman with a history of severe allergic asthma that progressively worsened over the years despite the best therapy. She had been hospitalized 35 times, including nine admissions to the respiratory intensive care unit due to severe exacerbations. To rule out other possible diagnoses, several investigations were performed, such as computed tomography scan of the chest and neck, fiberoptic laryngoscopy, antineutrophil cytoplasmic antibodies, and complete blood cell count...
2017: Therapeutics and Clinical Risk Management
Christopher C Cheung, Maggie Constantine, Amir Ahmadi, Carolyn Shiau, Luke Y C Chen
Persistent eosinophilia can cause cardiac tissue damage, typically in the form of eosinophilic myocarditis, whether the underlying cause is reactive, a clonal myeloid disorder, or idiopathic hypereosinophilic syndrome (HES). Eosinophilic myocarditis ranges from mild localized disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. Systemic treatment varies widely depending on the underlying cause, so thorough investigation and precise diagnosis are essential...
November 2017: American Journal of the Medical Sciences
Lakshmi Kallur, Alexei Gonzalez-Estrada, Frank Eidelman, Ves Dimov
Mepolizumab is a humanized monoclonal antibody that binds to and inactivates IL-5. It is available as a subcutaneous preparation. The practical application of mepolizumab is as an add-on therapy in the treatment of severe eosinophilic asthma. Areas covered: This article was created from a comprehensive literature search with information taken from meta-analyses, systematic reviews, and clinical trials of adults. The articles that have been selected evaluate the use of mepolizumab and its role in eosinophilic asthma...
December 2017: Expert Opinion on Drug Metabolism & Toxicology
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
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
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
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...
December 2017: Allergologia et Immunopathologia
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...
January 30, 2018: Journal of Pharmaceutical and Biomedical Analysis
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