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https://www.readbyqxmd.com/read/28530020/golimumab-a-review-in-inflammatory-arthritis
#1
James E Frampton
Golimumab (Simponi(®)), a fully human monoclonal antibody against tumour necrosis factor-alpha (TNFα), is given once monthly by subcutaneous injection. In the EU, golimumab is approved as monotherapy and/or in combination with methotrexate for the treatment of inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis [comprising ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] in adults, and polyarticular juvenile idiopathic arthritis (pJIA) in children...
May 22, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28529918/advances-in-dyslipidemia-management-for-prevention-of-atherosclerosis-pcsk9-monoclonal-antibody-therapy-and-beyond
#2
REVIEW
Nathan D Wong, Paul D Rosenblit, Robert S Greenfield
In 2003, select families with familial hypercholesterolemia were first identified to have gain-of-function mutations for proprotein convertase subtilisin kexin type 9 (PCSK9) followed, in 2006, by the identification of those with lifelong low levels of LDL-C and lowered atherosclerotic cardiovascular disease (ASCVD) risk who had loss-of-function PCSK9 mutations. These discoveries led to the rapid development of PSCK9-targeted monoclonal antibody (PCSK9 mAb) therapies and, in 2015, 2 'fully-humanized' PCSK9 mAbs (alirocumab and evolocumab) were marketed in the United States, Europe, and other countries...
April 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28528528/ustekinumab-a-review-in-moderate-to-severe-crohn-s-disease
#3
Yvette N Lamb, Sean T Duggan
Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists...
May 20, 2017: Drugs
https://www.readbyqxmd.com/read/28528519/il-6-blockade-in-the-management-of-non-infectious-uveitis
#4
Giuseppe Lopalco, Claudia Fabiani, Jurgen Sota, Orso Maria Lucherini, Gian Marco Tosi, Bruno Frediani, Florenzo Iannone, Mauro Galeazzi, Rossella Franceschini, Donato Rigante, Luca Cantarini
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases...
May 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28527859/tackling-influenza-with-broadly-neutralizing-antibodies
#5
REVIEW
Davide Corti, Elisabetta Cameroni, Barbara Guarino, Nicole L Kallewaard, Qing Zhu, Antonio Lanzavecchia
Monoclonal antibodies have revolutionized the treatment of several human diseases, including cancer, autoimmunity and inflammatory conditions and represent a new frontier for the treatment of infectious diseases. In the last decade, new methods have allowed the efficient interrogation of the human antibody repertoire from influenza immune individuals and the isolation of several monoclonal antibodies capable of dealing with the high variability of influenza viruses. Here, we will provide a comprehensive overview of the specificity, antiviral and immunological mechanisms of action and development into the clinic of broadly reactive monoclonal antibodies against influenza A and B viruses...
May 18, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28527704/anti-madcam-antibody-pf-00547659-for-ulcerative-colitis-turandot-a-phase-2-randomised-double-blind-placebo-controlled-trial
#6
Séverine Vermeire, William J Sandborn, Silvio Danese, Xavier Hébuterne, Bruce A Salzberg, Maria Klopocka, Dino Tarabar, Tomas Vanasek, Miloš Greguš, Paul A Hellstern, Joo Sung Kim, Miles P Sparrow, Kenneth J Gorelick, Michelle Hinz, Alaa Ahmad, Vivek Pradhan, Mina Hassan-Zahraee, Robert Clare, Fabio Cataldi, Walter Reinisch
BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy...
May 17, 2017: Lancet
https://www.readbyqxmd.com/read/28527063/the-role-of-anti-cgrp-antibodies-in-the-pathophysiology-of-primary-headaches
#7
Piero Barbanti, Cinzia Aurilia, Luisa Fofi, Gabriella Egeo, Patrizia Ferroni
Calcitonin gene-related peptide (CGRP), a potent vasodilator and pain-signaling neuropeptide, is a validated therapeutic target for migraine and cluster headache. Four anti-CGRP monoclonal antibodies (mAbs) have been developed, representing the first specific, mechanism-based, migraine prophylactic treatment. CGRP mAbs demonstrated good efficacy coupled to excellent tolerability and safety in 5 phase II clinical trials. Notably, CGRP mAbs induced complete migraine remission in a patients' subset. To date, more than 20 phase III trials using CGRP mAbs for of episodic and chronic migraine and cluster headache prevention are ongoing...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28527055/cluster-headache-present-and-future-therapy
#8
Massimo Leone, Alessandro Giustiniani, Alberto Proietti Cecchini
Cluster headache is characterized by severe, unilateral headache attacks of orbital, supraorbital or temporal pain lasting 15-180 min accompanied by ipsilateral lacrimation, rhinorrhea and other cranial autonomic manifestations. Cluster headache attacks need fast-acting abortive agents because the pain peaks very quickly; sumatriptan injection is the gold standard acute treatment. First-line preventative drugs include verapamil and carbolithium. Other drugs demonstrated effective in open trials include topiramate, valproic acid, gabapentin and others...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28527051/new-treatments-for-headache
#9
Kasra Maasumi, Stewart J Tepper, Alan M Rapoport
Headache disorders are common worldwide and often disabling. Until recently, treatments were borrowed from other branches of neurology and medicine. Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) ligand and receptor, small molecule CGRP receptor antagonist gepants, serotonin1F agonists, new devices to deliver currently available drugs, and neuromodulation devices have recently been in the forefront of headache treatments that are rather specific for various headache disorders. These novel therapies are changing the field of headache medicine...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526278/biotherapeutics-in-chronic-rhinosinusitis-with-and-without-nasal-polyps
#10
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/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#11
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525647/evaluation-of-the-effects-of-tanezumab-a-monoclonal-antibody-against-nerve-growth-factor-on-the-sympathetic-nervous-system-in-adult-cynomolgus-monkeys-macaca-fascicularis-a-stereologic-histomorphologic-and-cardiofunctional-assessment
#12
Patrice Belanger, Paul Butler, Mark Butt, Siddhartha Bhatt, Stephen Foote, David Shelton, Mark Evans, Rosalinda Arends, Susan Hurst, Carlin Okerberg, Thomas Cummings, David Potter, Jill Steidl-Nichols, Mark Zorbas
Tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. Three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (SNS) of adult nonhuman primates. Study 1 evaluated potential effects of subcutaneous (SC) tanezumab (1.2 mg/kg every 8 weeks [Q8W]) on SNS in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a non-dosing/recovery period...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28524152/-vascular-endothelial-growth-factor-inhibitors-in-the-treatment-of-neovascular-age-related-macular-degeneration
#13
I N Dyakov, S K Zyryanov
Neovascular age-related macular degeneration (AMD) is the leading cause of vision loss in older patients. An important role in angiogenesis is played by regulatory mechanisms (an increase in the number of proliferating endothelial and stromal cells and morphological alterations in the vascular network) induced by factors from the vascular endothelial growth factor (VEGF) family. Since 2006, the key treatment of neovascular AMD includes agents that inhibit the activity of VEGF. This review covers the effectiveness and safety of the use of anti-VEGF agents in neovascular AMD patients...
2017: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/28523957/clinical-case-idelalisib-induced-immunoglobulin-flare
#14
Jan Novak, Martin Havrda, Lubica Gaherova, Jan Spicka, Tomas Kozak
IgM flare is a transient, treatment-induced, increase of monoclonal IgM levels in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) patients. Until recently this phenomenon was observed in patients treated with Cladribine and Rituximab. Here we report a case of a heavily pretreated chronic lymphocytic leukemia patient with an atypically high immunoglobulin production who developed clinically significant immunoglobulin flare following Idelalisib treatment.
May 19, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28523951/launching-biosimilar-rituximab-an-industry-opinion-on-biosimilar-uptake-in-europe
#15
Richard Trollope, Sue Johnson, Henry Ireland
Richard Trollope and Sue Johnson talk with Henry Ireland, Senior Editor about the recent approval of biosimilar rituximab (Truxima(®)) & the current state of biosimilar uptake across Europe Richard Trollope, Head of Biosimilars, Mundipharma International Limited, qualified as a biochemist before joining Wyeth's commercial operations, prior to its acquisition by Pfizer. Richard later joined Yamanouchi Pharmaceuticals (now Astellas Pharma). His fascination with oncology led him to join Mundipharma in Europe and after joining the company's UK arm (Napp Pharmaceuticals Limited), Richard began his journey in biosimilars...
May 19, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28523586/ocrelizumab-first-global-approval
#16
James E Frampton
Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS...
June 2017: Drugs
https://www.readbyqxmd.com/read/28522957/crohn-s-disease-and-smoldering-multiple-myeloma-a-case-report-and-literature-review
#17
So Young Park, Jae Min Kim, Hyun Joon Kang, Minje Kim, Jae Joon Han, Chi Hoon Maeng, Sun Kyung Baek, Hwi-Joong Yoon, Si-Young Kim, Hyo Jong Kim
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy...
April 2017: Intestinal Research
https://www.readbyqxmd.com/read/28521478/enhancement-of-antitumor-immunity-by-combination-of-anti-ctla-4-antibody-and-radioimmunotherapy-through-the-suppression-of-tregs
#18
Cheol-Hun Son, Jaeho Bae, Hong-Rae Lee, Kwangmo Yang, You-Soo Park
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the in vivo immune suppressive functions of CTLA-4 are mediated only by a reduction in the level of conventional T-cell activity, or enhancement of Treg function...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28518088/in-vitro-methods-for-comparing-target-binding-and-cdc-induction-between-therapeutic-antibodies-applications-in-biosimilarity-analysis
#19
Nohemi Salinas-Jazmín, Edith González-González, Luz X Vásquez-Bochm, Sonia M Pérez-Tapia, Marco A Velasco-Velázquez
Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of different pathologies, including cancers. The development of biosimilar mAbs by pharmaceutical companies is a market opportunity, but it is also a strategy to increase drug accessibility and reduce therapy-associated costs. The protocols detailed here describe the evaluation of target binding and CDC induction by rituximab in Daudi cells. These two functions require different structural regions of the antibody and are relevant to the clinical effect induced by rituximab...
May 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516874/long-term-effects-of-interleukin-17a-inhibition-with-secukinumab-in-active-ankylosing-spondylitis-3-year-efficacy-and-safety-results-from-an-extension-of-the-phase-3-measure-1-trial
#20
Xenofon Baraliakos, Alan J Kivitz, Atul A Deodhar, Jürgen Braun, James C Wei, Eumorphia Maria Delicha, Zsolt Talloczy, Brian Porter
OBJECTIVES: Secukinumab, a fully human anti-IL-17A monoclonal antibody, provided rapid and sustained improvements in signs and symptoms of ankylosing spondylitis (AS) over 2 years in the Phase 3 MEASURE 1 trial. Here, we report efficacy and safety after 3 years of treatment. METHODS: AS subjects completing 2 years of treatment every 4 weeks with subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) entered a separate 3-year extension study (NCT01863732)...
May 15, 2017: Clinical and Experimental Rheumatology
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