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Garry M Walsh
A marked heterogeneity is exhibited by asthma both clinically and at the molecular level with different phenotypes driven by diverse mechanistic pathways that require specifically targeted treatments. Biologics aimed at IL-4/13, IL-5 or IgE are proven or potentially effective treatments for patients with difficult to treat eosinophilic asthma. Importantly, it is now widely accepted that biologic-based therapies give significant clinical improvements in those patient populations where asthma phenotypes are taken into account...
March 20, 2018: Immunotherapy
Merin Kuruvilla
Hypereosinophilic syndrome (HES) is a rare disease defined by organ damage directly attributable to hypereosinophilia that is either primary (neoplastic), secondary (reactive) or idiopathic. The mainstay of therapy in idiopathic HES centers around systemic steroids, and cytoreduction with hydroxyurea and interferon-alfa in steroid refractory cases. We describe the successful treatment of recalcitrant, idiopathic cutaneous HES with reslizumab, a humanized interleukin-5 blocker.
February 26, 2018: Annals of Allergy, Asthma & Immunology
Mario Cazzola, Maria Gabriella Matera, Francesca Levi-Schaffer, Paola Rogliani
Reslizumab, a humanized mAb against IL-5, reduces the number of eosinophils in the blood and lungs. Based on efficacy and safety data from pivotal RCTs, reslizumab had been approved for use as an add-on maintenance treatment of severe asthma with an eosinophilic phenotype in adults who have a history of exacerbations despite receiving their current asthma medicines. Areas covered: Current literature on reslizumab has been reviewed with a specific focus on its safety profile in the treatment of severe asthma...
February 27, 2018: Expert Opinion on Drug Safety
Anna Bondar, Megan Carr
No abstract text is available yet for this article.
November 15, 2017: American Family Physician
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
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
Jonathan E Markowitz, Laura Jobe, Michelle Miller, Carrie Frost, Zegilor Laney, Ransome Eke
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease characterized by infiltration of eosinophils in the esophageal epithelium. There are limited treatment options for EoE. RATIONALE: To evaluate the long term safety and efficacy of reslizumab (RSZ) in pediatric patients who received RSZ in a randomized controlled trial (RCT) and expanded access program. METHODS: Records of patients who received RSZ in our center were reviewed. Patients received RSZ 2 mg/kg (or placebo) every 4 weeks as part of the RCT, open label extension (OLE), and compassionate use (CU)...
November 22, 2017: Journal of Pediatric Gastroenterology and Nutrition
Kevin Murphy, Joshua Jacobs, Leif Bjermer, John M Fahrenholz, Yael Shalit, Margaret Garin, James Zangrilli, Mario Castro
BACKGROUND: In placebo-controlled trials, reslizumab, an anti-IL-5 monoclonal antibody, significantly reduced asthma exacerbations and improved lung function and asthma control in patients with eosinophilic asthma. OBJECTIVE: This open-label extension study evaluated safety and efficacy of reslizumab for up to 24 months. METHODS: After participation in 1 of 3 placebo-controlled, phase III trials in moderate-to-severe eosinophilic asthma, patients received reslizumab 3...
November 2017: Journal of Allergy and Clinical Immunology in Practice
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
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...
January 2018: Current Opinion in Pulmonary Medicine
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
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
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
M Maurer, S Altrichter, M Metz, T Zuberbier, M K Church, K-C Bergmann
No abstract text is available yet for this article.
September 19, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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
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
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
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