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Il 13 antibody severe asthma

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https://www.readbyqxmd.com/read/29108767/biologics-in-the-treatment-of-severe-asthma
#1
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/29068539/eosinophil-persistence-in-vivo-and-sustained-viability-ex-vivo-in-response-to-respiratory-challenge-with-fungal-allergens
#2
Wendy E Geslewitz, Caroline M Percopo, Helene F Rosenberg
BACKGROUND: Eosinophils are immunomodulatory leukocytes that contribute to the pathogenesis of Th2 driven asthma and allergic lung diseases. OBJECTIVE: Our goal was to identify unique properties of eosinophils recruited to the lungs and airways of mice in response to challenge with asthma-associated fungal allergens. METHODS: Mice were challenged intranasally on days 0, 3 and 6 with a filtrate of Alternaria alternata. Recruited eosinophils were enumerated in bronchoalveolar lavage fluid...
October 25, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28990423/dupilumab-for-the-treatment-of-asthma
#3
Corrado Pelaia, Alessandro Vatrella, Luca Gallelli, Rosa Terracciano, Paolo Navalesi, Rosario Maselli, Girolamo Pelaia
Dupilumab is a fully human IgG4 monoclonal antibody directed against the α subunit of the interleukin (IL)-4 receptor (IL-4Rα). Since the activation of IL-4Rα is utilized by both IL-4 and IL-13 to mediate their pathophysiological effects, dupilumab behaves as a dual antagonist of these two sister cytokines, which blocks IL-4/IL-13-dependent signal transduction. Areas covered: Herein, the authors review the cellular and molecular pathways activated by IL-4 and IL-13, which are relevant to asthma pathobiology...
October 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28979129/dupilumab-in-the-management-of-moderate-to-severe-asthma-the-data-so-far
#4
REVIEW
Pilar Barranco, Elsa Phillips-Angles, Javier Dominguez-Ortega, Santiago Quirce
Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies - particularly, selective targeted monoclonal antibodies (mAbs)...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28948572/overlapping-effects-of-new-monoclonal-antibodies-for-severe-asthma
#5
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/28910970/antibody-therapy-for-the-management-of-severe-asthma-with-eosinophilic-inflammation
#6
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/28888244/new-and-anticipated-therapies-for-severe-asthma
#7
Stephen P Peters, William W Busse
Asthma is frequently undertreated, resulting in a relatively high prevalence of patients with uncontrolled disease, characterized by the presence of symptoms and risk of adverse outcomes. Patients with uncontrolled asthma have a higher risk of morbidity and mortality, underscoring the importance of identifying uncontrolled disease and modifying management plans to improve control. Several assessment tools exist to evaluate control with various cutoff points and measures, but these tools do not reliably correlate with physiological measures and should be considered a supplement to physiological tests...
September 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28843617/model-based-clinical-pharmacology-profiling-and-exposure-response-relationships-of-the-efficacy-and-biomarker-of-lebrikizumab-in-patients-with-moderate-to-severe-asthma
#8
Rui Zhu, Yanan Zheng, Nathanael L Dirks, Shweta Vadhavkar, Jin Yan Jin, Kun Peng, Cecile T J Holweg, Julie Olsson, John G Matthews, Wendy S Putnam
Lebrikizumab is a humanized monoclonal antibody that binds to interleukin-13 and has been evaluated as a treatment for moderate-to-severe asthma. Objectives of this work were to characterize lebrikizumab pharmacokinetics (PK), identify influential covariates, and graphically explore exposure-response relationships in moderate-to-severe asthmatics. Pooled PK data from 11 studies were used in the population PK model development. Full covariate modeling was used to evaluate the impact of pre-specified covariates...
October 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28830530/prenatal-tobacco-smoke-exposure-predisposes-offspring-mice-to-exacerbated-allergic-airway-inflammation-associated-with-altered-innate-effector-function
#9
Maria Ferrini, Sophia Carvalho, Yoon Hee Cho, Britten Postma, Lucas Miranda Marques, Kent Pinkerton, Kevan Roberts, Zeina Jaffar
BACKGROUND: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma...
August 22, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28758192/dose-exposure-response-relationship-of-the-investigational-anti-il-13-monoclonal-antibody-tralokinumab-in-patients-with-severe-uncontrolled-asthma
#10
P Baverel, N White, P Vicini, M O Karlsson, B Agoram
Interleukin (IL)-13 is involved in the pathogenesis of some types of asthma. Tralokinumab is a human IgG4 monoclonal antibody that specifically binds to IL-13. Two placebo-controlled Phase 2 studies (Phase 2a, NCT00873860 and Phase 2b, NCT01402986) have been conducted in which tralokinumab was administered subcutaneously (SC). This investigation aimed to characterize tralokinumab's dose-exposure-response (forced expiratory volume in one second [FEV1 ]) relationship in patients with asthma and to predict the most appropriate dose for Phase 3...
July 30, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28751233/sputum-autoantibodies-in-patients-with-severe-eosinophilic-asthma
#11
Manali Mukherjee, David C Bulir, Katherine Radford, Melanie Kjarsgaard, Chynna Margaret Huang, Elizabeth A Jacobsen, Sergei I Ochkur, Ana Catuneanu, Hanah Lamothe-Kipnes, James Mahony, James J Lee, Paige Lacy, Parameswaran K Nair
BACKGROUND: The persistence of eosinophils in sputum despite high doses of corticosteroids indicates disease severity in asthmatic patients. Chronic inflamed airways can lose tolerance over time to immunogenic entities released on frequent eosinophil degranulation, which further contributes to disease severity and necessitates an increase in maintenance corticosteroids. OBJECTIVES: We sought to investigate the possibility of a polyclonal autoimmune event in the airways of asthmatic patients and to identify associated clinical and molecular characteristics...
July 24, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28696336/perspectives-on-exhaled-nitric-oxide
#12
Fabio Luigi Massimo Ricciardolo, Philip E Silkoff
The history of nitric oxide (NO) in respiratory field dates back to the beginning of '90s with the ancestral study by Lars Gustafsson et al. describing the presence of endogenous NO in the exhaled breath of human beings. Soon after, independent studies showed that exhaled NO concentrations (FENO) is higher in asthmatics than in normal subjects. Not all asthmatics demonstrate a high FENO reflecting heterogeneity of asthma. High values of FENO are associated with over-expression of corticosteroid-sensitive iNOS isoform and allergic/eosinophilic inflammation...
July 11, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28584245/immune-signatures-of-pathogenesis-in-the-peritoneal-compartment-during-early-infection-of-sheep-with-fasciola-hepatica
#13
Maria Teresa Ruiz-Campillo, Veronica Molina Hernandez, Alejandro Escamilla, Michael Stevenson, Jose Perez, Alvaro Martinez-Moreno, Sheila Donnelly, John P Dalton, Krystyna Cwiklinski
Immune signatures of sheep acutely-infected with Fasciola hepatica, an important pathogen of livestock and humans were analysed within the peritoneal compartment to investigate early infection. Within the peritoneum, F. hepatica antibodies coincided with an intense innate and adaptive cellular immune response, with infiltrating leukocytes and a marked eosinophilia (49%). However, while cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated, these were not statistically different at 18 days post-infection compared to uninfected animals indicating that the immune response is muted and not yet skewed to a Th2 type response that is associated with chronic disease...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28583618/new-anti-eosinophil-drugs-for-asthma-and%C3%A2-copd-targeting-the-trait
#14
REVIEW
Elisabeth H Bel, Anneke Ten Brinke
Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait...
June 2, 2017: Chest
https://www.readbyqxmd.com/read/28547386/dupilumab-first-global-approval
#15
REVIEW
Matt Shirley
Dupilumab (Dupixent(®)) is a fully human monoclonal antibody directed against the interleukin (IL)-4 receptor α (IL-4Rα) subunit. Dupilumab inhibits the signalling of the type 2 cytokines IL-4 and IL-13 and was co-developed by Regeneron Pharmaceuticals and Sanofi as a potential therapeutic agent for the treatment of atopic or allergic diseases. In March 2017 dupilumab received its first global approval, in the USA, for use in the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable...
July 2017: Drugs
https://www.readbyqxmd.com/read/28526278/biotherapeutics-in-chronic-rhinosinusitis-with-and-without-nasal-polyps
#16
Claus Bachert, Philippe Gevaert, Peter Hellings
In western countries, 85% of chronic rhinosinusitis with nasal polyp disease reveals a type 2 inflammatory pattern with expression of IL-4, -5, and -13 as well as increased concentrations of IgE, whereas chronic rhinosinusitis without nasal polyps merely expresses these biomarkers. The degree of type 2 inflammation furthermore is associated with disease severity, asthma comorbidity, and recurrence of disease after surgery. Therefore, these biomarkers also form the targets for innovative therapeutic approaches such as monoclonal antibodies directed against IgE, IL-5, and IL-4 receptor alpha, blocking the activity of IL-4 and -13...
May 16, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28479600/a-crucial-role-of-the-pd-1h-coinhibitory-receptor-in-suppressing-experimental-asthma
#17
Huafeng Liu, Xin Li, Li Hu, Min Zhu, Bailin He, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation...
May 8, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28427296/predictors-of-response-to-therapy-with-omalizumab-in-patients-with-severe-allergic-asthma-a-real-life-study
#18
Maria Kallieri, Andriana I Papaioannou, Evgenia Papathanasiou, Polyxeni Ntontsi, Spyridon Papiris, Stelios Loukides
OBJECTIVES: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. METHODS: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center...
August 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28287273/novel-monoclonal-treatments-in-severe-asthma
#19
Howraman Meteran, Hanieh Meteran, Celeste Porsbjerg, Vibeke Backer
AIM: To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. DATA SOURCES: We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." STUDY SELECTIONS: Only articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies...
March 13, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28277826/commonality-of-the-il-4-il-13-pathway-in-atopic-diseases
#20
Namita A Gandhi, Gianluca Pirozzi, Neil M H Graham
Allergy results from an aberrant Type 2 inflammatory response, triggered by a wide range of environmental antigens (allergens) that lead to various immune responses, culminating in the production of immunoglobulin E (IgE). Two key cytokines, interleukin (IL)-4 and IL-13, are critical to the induction and perpetuation of the Type 2 response, and have been implicated in multiple atopic diseases. Area covered: This review summarizes recent milestone developments that have elucidated components of the pathogenesis of atopic diseases such as atopic dermatitis (AD), asthma, and chronic sinusitis with nasal polyposis (CSwNP)...
May 2017: Expert Review of Clinical Immunology
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