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https://www.readbyqxmd.com/read/28535776/the-role-of-anti-ige-omalizumab-xolair-in-the-management-of-severe-recalcitrant-paediatric-atopic-eczema-adapt-statistical-analysis-plan
#1
Tao Chen, Susan Chan, Gideon Lack, Suzie Cro, Victoria R Cornelius
BACKGROUND: The Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT) is a trial to determine the clinical efficacy and safety of omalizumab for children with severe atopic eczema. This article describes the detailed statistical analysis plan for the ADAPT as an update to the published protocol and is submitted prior to knowing all outcomes. METHOD AND DESIGN: The ADAPT is a randomised, double-blind, placebo-controlled trial with a primary objective to determine whether anti-IgE reduces eczema severity as assessed by the validated eczema score (objective SCORAD) after 24 weeks of treatment in children with severe eczema...
May 23, 2017: Trials
https://www.readbyqxmd.com/read/28517027/lung-function-parameters-in-omalizumab-responder-patients-an-interesting-tool
#2
F Paganin, G Mangiapan, A Proust, A Prudhomme, J Attia, S Marchand-Adam, F Pellet, F Milhe, B Melloni, A Bernady, C Raspaud, C Nocent, P Berger, L Guilleminault
BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and non-responder patients remain inconclusive. The objective of this real-life study was to compare the changes in FEV1 of omalizumab responders and non-responders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions...
May 18, 2017: Allergy
https://www.readbyqxmd.com/read/28516039/a-plane-screw-fixation-is-a-nidus-for-paecilomyces-sinusitis-in-a-patient-with-aspirin-exacerbated-respiratory-disease
#3
Anthony M Szema, Cyrus Jo
Titanium plane screw fixation of the frontal sinus is an approach used by otolaryngologists to obliterate this space in an attempt to reduce sinus infections. In this case, however, the titanium used became a nidus of infection which cultured the fungus Paecilomyces. The patient also had a hypersensitivity reaction to mold with positive skin tests and IgE, as well as eosinophilic esophagitis. Treatment entailed anti-fungals, anti-IgE, and fungal immunotherapy to multiple fungal antigens prevalent to the geographic region...
2017: IDCases
https://www.readbyqxmd.com/read/28483235/basophil-activation-test-for-inhalant-allergens-in-pediatric-patients-with-allergic-rhinitis
#4
Ismail Ogulur, Ayca Kiykim, Safa Baris, Ahmet Ozen, Ezgi Gizem Yuce, Elif Karakoc-Aydiner
OBJECTIVE: Flow cytometric quantification of in vitro basophil activation can be quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. Current study aimed to evaluate the clinical relevance of basophil activation test (BAT) for the diagnosis of pediatric grass pollen and house dust mite (HDM) allergies. METHODS: Forty-seven patients suffering from allergic rhinitis with HDM and grass pollen co-sensitization with clinical history of allergic rhinitis and/or asthma and 15 non-allergic healthy subjects were enrolled...
June 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28464704/prospects-for-new-and-emerging-therapeutics-in-severe-asthma-the-role-of-biologics
#5
Seçil Kepil Özdemir, Sevim Bavbek
Asthma is a common and heterogeneous disease. While current conventional therapies are effective in the majority of the patients, a significant subgroup remain uncontrolled despite these treatments. Different biological agents are currently approved or undergoing development for treatment of asthma, including anti-IgE, anti-interleukin (IL)-5, anti-IL-13, anti-IL-4 and anti-thymic stromal lymphopoietin agents. This review will focus on the currently available evidence regarding the new and emerging biological agents in severe asthma...
May 10, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28442583/seletalisib-characterization-of-a-novel-potent-and-selective-inhibitor-of-pi3k%C3%AE
#6
Rodger A Allen, Daniel C Brookings, Mark J Powell, Jean Delgado, Lindsay K Shuttleworth, Mark Merriman, Ian J Fahy, Roohi Tewari, John P Silva, Louise J Healy, Gareth C G Davie, Breda Twomey, Rona M Cutler, Apoorva Kotian, Andrea Crosby, Gillian McCluskey, Gillian Watt, Andrew Payne
PI3Ks are key signaling enzymes regulating cellular survival, development and function. Expression of the PI3Kδ isoform is largely restricted to leukocytes and it plays a key role in immune cell development and function. Seletalisib is a novel small molecule inhibitor of PI3Kδ that was evaluated in biochemical assays, cellular assays of adaptive and innate immunity, and an in vivo rat model of inflammation. Our findings show that seletalisib is a potent, ATP-competitive and highly selective PI3Kδ inhibitor able to block AKT phosphorylation following activation of the BCR in a B-cell line...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28441991/in-vitro-impact-of-anti-immunoglobulin-e-monoclonal-antibodies-including-omalizumab-on-whole-blood-basophil-histamine-release-assessment-of-direct-induction-of-basophil-histamine-release-and-evaluation-of-modulation-of-allergen-induced-basophil-histamine-release
#7
Krzysztof Kowal, Pawel Bielecki, Ilona V DuBuske, Lawrence M DuBuske
AIM: The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated. METHODS: Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens...
May 1, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28439933/effect-of-anti-ige-in-occupational-asthma-caused-by-exposure-to-low-molecular-weight-agents
#8
M Ollé-Monge, M J Cruz, S Gomez-Ollés, I Ojanguren, J Vanoirbeek, X Muñoz
BACKGROUND: The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In the present study we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts. METHODS: On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18 and 21 animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline...
April 25, 2017: Allergy
https://www.readbyqxmd.com/read/28438838/allosteric-mechanism-of-action-of-the-therapeutic-anti-ige-antibody-omalizumab
#9
Anna M Davies, Elizabeth G Allan, Anthony H Keeble, Jean Delgado, Benjamin P Cossins, Alkistis N Mitropoulou, Marie O Y Pang, Tom Ceska, Andrew J Beavil, Graham Craggs, Marta Westwood, Alistair J Henry, James M McDonnell, Brian J Sutton
Immunoglobulin E and its interactions with receptors FcϵRI and CD23 play a central role in allergic disease. Omalizumab, a clinically-approved therapeutic antibody, inhibits the interaction between IgE and FcϵRI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cϵ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only partially bent, with large-scale conformational changes in the Cϵ3 domains that inhibit the interaction with FcϵRI...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28435464/clinical-efficacy-of-omalizumab-in-chronic-spontaneous-urticaria-is-associated-with-a-reduction-of-fc%C3%AE%C2%B5ri-positive-cells-in-the-skin
#10
Martin Metz, Petra Staubach, Andrea Bauer, Randolf Brehler, Janine Gericke, Michael Kangas, Joanna Ashton-Chess, Philip Jarvis, Panayiotis Georgiou, Janice Canvin, Rainer Hillenbrand, Veit J Erpenbeck, Marcus Maurer
Background. Treatment with omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of omalizumab on levels of high affinity IgE receptor-positive (FcεRI(+)) and IgE-positive (IgE(+)) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks...
2017: Theranostics
https://www.readbyqxmd.com/read/28429307/emerging-approaches-to-food-desensitization-in-children
#11
REVIEW
Ahmad Hamad, Wesley A Burks
PURPOSE OF REVIEW: The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy. RECENT FINDINGS: Recent advancements in epicutaneous, sublingual, and oral immunotherapy for food allergy in the future may offer children with food allergy and their families a viable option to reduce risk or severity of anaphylaxis with phase III trials ongoing for two of these treatment modalities. Food allergy prevalence in children is estimated to be up to 8%...
May 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28427296/predictors-of-response-to-therapy-with-omalizumab-in-patients-with-severe-allergic-asthma-a-real-life-study
#12
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...
April 28, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28401621/mouse-models-of-severe-asthma-understanding-the-mechanisms-of-steroid-resistance-tissue-remodelling-and-disease-exacerbation
#13
REVIEW
Steven Maltby, Hock L Tay, Ming Yang, Paul S Foster
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e...
April 11, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28396318/blocking-allergic-reaction-through-targeting-surface-bound-ige-with-low-affinity-anti-ige-antibodies
#14
Ke Zhang, Jeffrey Liu, Thao Truong, Elyssa Zukin, Wendy Chen, Andrew Saxon
Allergic disorders have now become a major worldwide public health issue, but the effective treatment options remain limited. We report a novel approach to block allergic reactivity by targeting the surface-bound IgE of the allergic effector cells via low-affinity anti-human IgE Abs with dissociation constants in the 10(-6) to 10(-8) M range. We demonstrated that these low-affinity anti-IgE mAbs bind to the cell surface-bound IgE without triggering anaphylactic degranulation even at high concentration, albeit they would weakly upregulate CD203c expression on basophils...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330497/atopic-dermatitis-anti-ige-paediatric-trial-adapt-the-role-of-anti-ige-in-severe-paediatric-eczema-study-protocol-for-a-randomised-controlled-trial
#15
Susan Chan, Victoria Cornelius, Tao Chen, Suzana Radulovic, Mandy Wan, Rahi Jahan, Gideon Lack
BACKGROUND: The evidence for systemic treatments for severe childhood eczema is limited and largely based on extrapolation of data from adult studies. Current therapies are often immunosuppressant and may be associated with both short- and long-term side effects. There is increasing in vitro and murine-model evidence for the role of IgE in the immunopathogenesis of atopic eczema. The aim of the study is to assess whether anti-IgE treatment (omalizumab) improves eczema, compared to placebo...
March 22, 2017: Trials
https://www.readbyqxmd.com/read/28328081/btk-inhibition-is-a-potent-approach-to-block-ige-mediated-histamine-release-in-human-basophils
#16
D Smiljkovic, K Blatt, G Stefanzl, Y Dorofeeva, C Skrabs, M Focke-Tejkl, W R Sperr, U Jaeger, R Valenta, P Valent
BACKGROUND: Recent data suggest that Bruton's tyrosine kinase (BTK) is an emerging therapeutic target in IgE receptor (IgER)-cross-linked basophils. METHODS: We examined the effects of four BTK inhibitors (ibrutinib, dasatinib, AVL-292, and CNX-774) on IgE-dependent activation and histamine release in blood basophils obtained from allergic patients (n=11) and nonallergic donors (n=5). In addition, we examined the effects of these drugs on the growth of the human basophil cell line KU812 and the human mast cell line HMC-1...
March 22, 2017: Allergy
https://www.readbyqxmd.com/read/28303277/basophil-fc%C3%AE%C2%B5ri-expression-in-chronic-spontaneous-urticaria-a-potential-immunological-predictor-of-response-to-omalizumab-therapy
#17
Gustavo Deza, Marta Bertolín-Colilla, Ramon M Pujol, Laia Curto-Barredo, Dulce Soto, Maribel García, Pilar Hernández, Ramon Gimeno, Ana M Giménez-Arnau
Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment...
March 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28294590/successful-omalizumab-treatment-in-hiv-positive-patient-with-chronic-spontaneous-urticaria-a-case-report
#18
E Iemoli, F Niero, L Borgonovo, M V Cossu, S Piconi
We described a case of a 56 year old homosexual HIV positive man who presented a history of CSU since one year (2012). All the allergologic, immunologic and microbiologic tests to evaluate the pathogenesis of wheals resulted negative. Therefore in June 2015 we decided to start therapy with Omalizumab while the patient kept on effective antiretroviral therapy with 310 cells/mm3 TCD4 counts and undetectable HIV viremia. After two monthly subcutaneuous injection of 150 mg of Omalizumab the patient had no more urticarial symptoms...
March 2017: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28293414/galectin-3-an-early-predictive-biomarker-of-modulation-of-airway-remodeling-in-patients-with-severe-asthma-treated-with-omalizumab-for-36%C3%A2-months
#19
Anna Maria Riccio, Pierluigi Mauri, Laura De Ferrari, Rossana Rossi, Dario Di Silvestre, Louise Benazzi, Alessandra Chiappori, Roberto Walter Dal Negro, Claudio Micheletto, Giorgio Walter Canonica
BACKGROUND: Bronchial asthma is a heterogeneous disease characterized by three cardinal features: chronic inflammation, variable airflow obstruction, and airway hyperresponsiveness. Asthma has traditionally been defined using nonspecific clinical and physiologic variables that encompass multiple phenotypes and are treated with nonspecific anti-inflammatory therapies. Based on the modulation of airway remodeling after 12 months of anti-immunoglobulin E (IgE) treatment, we identified two phenotypes (omalizumab responder, OR; and non-omalizumab responder, NOR) and performed morphometric analysis of bronchial biopsy specimens...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/28287273/novel-monoclonal-treatments-in-severe-asthma
#20
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
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