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https://www.readbyqxmd.com/read/29611207/immunological-and-hematological-effects-of-il-5-r%C3%AE-targeted-therapy-an-overview
#1
REVIEW
M Hassani, L Koenderman
IL-5 is an important cytokine for priming and survival of mature eosinophils, and for proliferation and maturation of their progenitors. Hence, IL-5(Rα) targeting will be increasingly used in diseases where eosinophils are the key immune effector cells such as eosinophilic asthma (EA), hyper eosinophilic syndrome (HES), eosinophilic esophagitis (EE) and eosinophilic granulomatosis with polyangitis (EGPA). Therefore, several neutralizing monoclonal antibodies directed against IL-5 (mepolizumab and reslizumab) and its receptor IL-5Rα (benralizumab) have found or will find their way to the clinic...
April 3, 2018: Allergy
https://www.readbyqxmd.com/read/29609004/emerging-biological-therapies-for-treating-chronic-obstructive-pulmonary-disease-a-pairwise-and-network-meta-analysis
#2
Paola Rogliani, Maria Gabriella Matera, Ermanno Puxeddu, Marco Mantero, Francesco Blasi, Mario Cazzola, Luigino Calzetta
Inflammation in chronic obstructive pulmonary disease (COPD) is often corticosteroid resistant and, thus, alternative anti-inflammatory approaches are needed. Since it is still not clear whether blocking specific pro-inflammatory factors may provide clinical benefit in COPD, we have performed a meta-analysis to quantify the impact of monoclonal antibodies (mABs) targeting the cytokine/chemokine-mediated inflammation in COPD. A pairwise and network meta-analyses were performed by extracting data from randomized clicnial trials on COPD concerning the impact of mABs vs...
March 30, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29606855/benralizumab-in-the-treatment-of-severe-asthma-design-development-and-potential-place-in-therapy
#3
REVIEW
Corrado Pelaia, Alessandro Vatrella, Andrea Bruni, Rosa Terracciano, Girolamo Pelaia
Asthma is a widespread and heterogeneous inflammatory disease of the airways, which is characterized by several different phenotypes and endotypes. In particular, eosinophilic airway inflammation is a common pathologic trait of both allergic and nonallergic asthma. The key cytokine responsible for maturation, activation, recruitment, and survival of eosinophils is interleukin (IL)-5, which is mainly produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells. Therefore, for uncontrolled patients with severe eosinophilic asthma, who are not fully responsive to corticosteroids, IL-5 represents a very important molecular target for add-on biological therapies...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29541868/selection-of-a-ligand-binding-neutralizing-antibody-assay-for-benralizumab-comparison-with-an-antibody-dependent-cell-mediated-cytotoxicity-adcc-cell-based-assay
#4
Yuling Wu, Ahmad Akhgar, Jia J Li, Binbing Yu, Cecil Chen, Nancy Lee, Wendy I White, Lorin K Roskos
Assessment of anti-drug antibodies (ADAs) for neutralizing activity is important for the clinical development of biopharmaceuticals. Two types of neutralizing antibody (NAb) assays (competitive ligand-binding assay [CLBA] and cell-based assay [CBA]) are commonly used to characterize neutralizing activities. To support the clinical development of benralizumab, a humanized, anti-interleukin-5 receptor α, anti-eosinophil monoclonal antibody, we developed and validated a CLBA and a CBA. The CLBA and CBA were compared for sensitivity, drug tolerance, and precision to detect NAbs in serum samples from clinical trials...
March 14, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29517082/benralizumab-for-the-treatment-of-asthma
#5
M G Matera, P Rogliani, L Calzetta, G W Canonica, M Cazzola
Benralizumab is a humanized monoclonal antibody directed at the a subunit of the interleukin-5 receptor (IL-5R) that is under clinical development. The binding of benralizumab with the alpha chain of IL-5R results in inhibition of hetero-oligomerization of alpha and beta subunits and thus no signal transduction occurs. Consequently, this inhibition prevents proliferation of eosinophils and basophils and the cascade of events following it. Several pivotal trials have documented that benralizumab reduces asthma exacerbation rates with a significant increase in time to the next exacerbation, statistically improves prebronchodilator forced expiratory volume in 1 second (FEV1) and disease-specific health-related quality of life, and is well tolerated in patients with severe asthma and blood eosinophil counts greater than or equal to 150 cells/mcL...
December 2017: Drugs of Today
https://www.readbyqxmd.com/read/29485975/benralizumab-fasenra-for-severe-eosinophilic-asthma
#6
(no author information available yet)
No abstract text is available yet for this article.
February 26, 2018: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/29467297/eosinophil-depletion-suppresses-radiation-induced-small-intestinal-fibrosis
#7
Naoki Takemura, Yosuke Kurashima, Yuki Mori, Kazuki Okada, Takayuki Ogino, Hideki Osawa, Hirosih Matsuno, Lamichhane Aayam, Satoshi Kaneto, Eun Jeong Park, Shintaro Sato, Kouta Matsunaga, Yusuke Tamura, Yasuo Ouchi, Yutaro Kumagai, Daichi Kobayashi, Yutaka Suzuki, Yoshichika Yoshioka, Junichi Nishimura, Masaki Mori, Ken J Ishii, Mark E Rothenberg, Hiroshi Kiyono, Shizuo Akira, Satoshi Uematsu
Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show that RIF is mediated by eosinophil interactions with α-smooth muscle actin-positive (α-SMA+ ) stromal cells. Abdominal irradiation caused RIF especially in the submucosa (SM) of the small intestine, which was associated with the excessive accumulation of eosinophils in both human and mouse. Eosinophil-deficient mice showed markedly ameliorated RIF, suggesting the importance of eosinophils...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29464664/benralizumab-first-global-approval
#8
A Markham
Kyowa Hakko Kirin, AstraZeneca and subsidiaries are developing benralizumab (Fasenra™)-a humanised anti-interleukin-5 receptor alpha chain (IL-5Rα) monoclonal antibody-as a treatment of severe eosinophilic asthma and chronic obstructive pulmonary disease (COPD). Eosinophilia is a characteristic of certain asthma and COPD phenotypes and depletion of eosinophils has demonstrated therapeutic benefit. Benralizumab was recently approved by the US FDA as add-on maintenance therapy for patients with severe asthma who have an eosinophilic phenotype...
March 2018: Drugs
https://www.readbyqxmd.com/read/29409951/benralizumab-efficacy-by-atopy-status-and-serum-immunoglobulin-e-for-patients-with-severe-uncontrolled-asthma
#9
Bradley E Chipps, Paul Newbold, Ian Hirsch, Frank Trudo, Mitchell Goldman
BACKGROUND: Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody being developed for patients with severe, uncontrolled asthma with eosinophilic inflammation. OBJECTIVE: To investigate the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) concentrations. METHODS: We analyzed pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) Phase III studies...
January 31, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29382593/benralizumab-attenuates-airway-eosinophilia-in-prednisone-dependent-asthma
#10
Roma Sehmi, Hui Fang Lim, Manali Mukherjee, Chynna Huang, Katherine Radford, Paul Newbold, Louis-Philippe Boulet, Delbert Dorscheid, James G Martin, Parameswaran Nair
No abstract text is available yet for this article.
January 31, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29359607/benralizumab-an-anti-il-5-receptor-%C3%AE-monoclonal-antibody-in-the-treatment-of-asthma
#11
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
https://www.readbyqxmd.com/read/29300693/antibodies-to-watch-in-2018
#12
Hélène Kaplon, Janice M Reichert
The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016...
February 2018: MAbs
https://www.readbyqxmd.com/read/29290671/pharmaceutical-approval-update
#13
Michele B Kaufman
Latanoprostene bunod ophthalmic solution (Vyzulta) for the reduction of intraocular pressure; letermovir (Prevymis) for prophylaxis of cytomegalovirus infection and disease after stem cell transplant; benralizumab (Fasenra) for the add-on maintenance treatment of severe asthma of an eosinophilic phenotype.
January 2018: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/29211545/efficacy-and-safety-of-benralizumab-for-eosinophilic-asthma-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#14
Bao-Ping Tian, Gen-Sheng Zhang, Jian Lou, Hong-Bin Zhou, Wei Cui
CONTEXT: Benralizumab is a humanized monoclonal antibody that targets the α chain of the IL-5 receptor (IL-5Rα) and is currently being assessed in clinical trials for asthma control. OBJECTIVE: Our systematic review and meta-analysis intends to evaluate the therapeutic efficacy and safety of benralizumab in patients with eosinophilic asthma. DATA SOURCES AND EXTRACTION: Literature searches of PubMed, Embase, and the Cochrane Library were performed to identify randomized controlled trials of benralizumab and clinic outcomes in asthmatics...
December 6, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29128192/efficacy-and-safety-of-benralizumab-in-japanese-patients-with-severe-uncontrolled-eosinophilic-asthma
#15
Ken Ohta, Mitsuru Adachi, Yuji Tohda, Tadashi Kamei, Motokazu Kato, J Mark Fitzgerald, Masayuki Takanuma, Tadahiro Kakuno, Nobuyuki Imai, Yanping Wu, Magnus Aurivillius, Mitchell Goldman
BACKGROUND: In the Phase III CALIMA trial, benralizumab significantly reduced asthma exacerbations, increased lung function, and alleviated symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate the efficacy and safety of benralizumab for Japanese patients in the CALIMA trial. METHODS: CALIMA was a randomised, controlled trial of 1306 patients (aged 12-75 years; registered at ClinicalTrials.gov: NCT01914757) with severe asthma uncontrolled by medium- to high-dosage inhaled corticosteroids and long-acting β2-agonists (ICS/LABA)...
November 8, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/29108767/biologics-in-the-treatment-of-severe-asthma
#16
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...
December 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
#17
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
https://www.readbyqxmd.com/read/29059087/controversies-and-opportunities-in-severe-asthma
#18
Marc Humbert, William Busse, Nicola A Hanania
PURPOSE OF REVIEW: Despite currently available treatments, many asthma patients remain inadequately controlled, but identifying distinct patient populations (phenotypes/endotypes) may optimize their management. This review discusses some of the controversies and opportunities for improved disease control in severe asthma. RECENT FINDINGS: Currently approved anti-immunoglobulin E and anti-interleukin 5 biologics, which target specific pathways instead of using a 'one size fits all' strategy, are efficacious and well tolerated therapies for severe asthma...
January 2018: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29049762/in-severe-asthma-benralizumab-reduced-daily-oral-glucocorticoid-dose-and-asthma-exacerbations-at-6-months
#19
COMMENT
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
#20
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/mm3 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
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