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https://www.readbyqxmd.com/read/27891572/safety-concerns-and-risk-management-of-multiple-sclerosis-therapies
#1
REVIEW
P Soelberg Sorensen
Currently, more than ten drugs have been approved for treatment of relapsing-remitting multiple sclerosis (MS). Newer treatments may be more effective, but have less favorable safety record. Interferon-β preparations and glatiramer acetate treatment require frequent subcutaneous or intramuscular injections and are only moderately effective, but have very rarely life-threatening adverse effects, whereas teriflunomide and dimethyl fumarate are administered orally and have equal or better efficacy, but have more potentially severe adverse effects...
November 27, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27888416/lesion-remyelinating-activity-of-gsk239512-versus-placebo-in-patients-with-relapsing-remitting-multiple-sclerosis-a-randomised-single-blind-phase-ii-study
#2
Caryl J Schwartzbach, Richard A Grove, Robert Brown, Debra Tompson, Florian Then Bergh, Douglas L Arnold
Histamine H3 receptor blockade may enhance lesion remyelination in multiple sclerosis (MS). The efficacy (using a magnetic resonance imaging marker of myelination, magnetisation transfer ratio [MTR]), safety and pharmacokinetics of GSK239512, a potent and brain penetrant H3 receptor antagonist/inverse agonist on lesion remyelination in relapsing-remitting MS (RRMS) were assessed. This was a phase II, randomised, parallel-group, placebo-controlled, double-blind (sponsor-unblinded), international, multicentre study (NCT01772199)...
November 25, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27880972/interferons-beta-versus-glatiramer-acetate-for-relapsing-remitting-multiple-sclerosis
#3
REVIEW
Loredana La Mantia, Carlo Di Pietrantonj, Marco Rovaris, Giulio Rigon, Serena Frau, Francesco Berardo, Anna Gandini, Anna Longobardi, Bianca Weinstock-Guttman, Alberto Vaona
BACKGROUND: Interferons-beta (IFNs-beta) and glatiramer acetate (GA) were the first two disease-modifying therapies (DMTs) approved 20 years ago for the treatment of multiple sclerosis (MS). DMTs' prescription rates as first or switching therapies and their costs have both increased substantially over the past decade. As more DMTs become available, the choice of a specific DMT should reflect the risk/benefit profile, as well as the impact on quality of life. As MS cohorts enrolled in different studies can vary significantly, head-to-head trials are considered the best approach for gaining objective reliable data when two different drugs are compared...
November 24, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27878443/real-world-effectiveness-of-natalizumab-and-fingolimod-compared-with-self-injectable-drugs-in-non-responders-and-in-treatment-na%C3%A3-ve-patients-with-multiple-sclerosis
#4
Luca Prosperini, Francesco Saccà, Cinzia Cordioli, Antonio Cortese, Fabio Buttari, Simona Pontecorvo, Assunta Bianco, Serena Ruggieri, Shalom Haggiag, Vincenzo Brescia Morra, Ruggero Capra, Diego Centonze, Giancarlo Di Battista, Elisabetta Ferraro, Ada Francia, Simonetta Galgani, Claudio Gasperini, Enrico Millefiorini, Massimiliano Mirabella, Carlo Pozzilli
In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis. As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i...
November 22, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27836182/myeloid-dendritic-cells-exhibit-defects-in-activation-and-function-in-patients-with-multiple-sclerosis
#5
Jürgen Haas, Alexander Schwarz, Mirjam Korporal-Kuhnke, Sven Jarius, Brigitte Wildemann
BACKGROUND: Regulatory T cells (Tregs) are functionally defective in patients with multiple sclerosis (MS) and this dysfunction is related to an imbalanced composition of naïve and memory Treg subtypes. Several lines of evidence indicate that these abnormalities might result from a premature decline in thymic-dependent Treg neogenesis. Myeloid dendritic cells (mDCs) critically determine Treg differentiation in the thymus, and thymic stromal lymphopoietin receptor (TSLPR) expressed on mDCs is a key component of the signaling pathways involved in this process...
November 2, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27836179/assessing-remyelination-metabolic-labeling-of-myelin-in-an-animal-model-of-multiple-sclerosis
#6
Rina Aharoni, Chava Rosen, Elias Shezen, Dekel D Bar-Lev, Ofra Golani, Yair Reisner, Michael Sela, Ruth Arnon
The lack of biomarkers is a major obstacle for investigating myelin repair. We used metabolic incorporation of the choline analog - propargyl-choline (P-Cho) to label and visualize newly synthesized myelin in the CNS of mice induced with experimental autoimmune encephalomyelitis (EAE). We further developed unbiased colocalization analysis to quantify P-Cho incorporation specifically into the myelin. Our findings indicate that P-Cho injection to mice recovering from EAE, either spontaneously or following glatiramer acetate treatment, results in significant elevation of its incorporation into the myelin, offering a novel strategy for assessing remyelination in animal models and the remyelination potential of candidate drugs...
November 1, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27829656/safety-and-efficacy-of-fingolimod-and-natalizumab-in-multiple-sclerosis-after-the-failure-of-first-line-therapy-single-center-experience-based-on-the-treatment-of-forty-four-patients
#7
Przemysław Puz, Anetta Lasek-Bal
BACKGROUND In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year. MATERIAL AND METHODS Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared...
November 10, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27828855/the-cross-reactivity-of-binding-antibodies-with-different-interferon-beta-formulations-used-as-disease-modifying-drugs-in-multiple-sclerosis-patients
#8
Agnieszka Wencel-Warot, Slawomir Michalak, Marcin Warot, Alicja Kalinowska-Lyszczarz, Radoslaw Kazmierski
Interferon beta (IFNb) preparations are commonly used as first-line therapy in relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by limited efficacy, partly due to the formation of anti-IFNb antibodies in patients.In this pilot study, we assessed with the ELISA method the presence of the binding antibodies (BAbs) against interferon beta after 2 years of therapy with subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were established again within 1 year after treatment withdrawal...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27824805/the-emerging-role-of-the-gut-microbiome-in-adult-patients-with-multiple-sclerosis
#9
Pamela K Newland, Margaret Heitkemper, Yanjiao Zhou
BACKGROUND: Approximately 2.3 million people worldwide are currently living with multiple sclerosis (MS). The pathophysiologic mechanism of MS is not well known. It has been suggested that alterations in the normal gut flora may contribute to MS etiology and symptoms. OBJECTIVE: The aims of this review are to describe the data suggesting a role for the gut microbiome in MS research and address its implications for practice. METHODS: A literature search of the following databases (PubMed, CINAHL, Cochrane library database, MEDLINE, Scopus, and Psychology and Behavioral Sciences) was conducted to find published studies relevant to gut microbiome in patients with MS...
December 2016: Journal of Neuroscience Nursing: Journal of the American Association of Neuroscience Nurses
https://www.readbyqxmd.com/read/27822961/the-cost-effectiveness-of-disease-modifying-therapies-for-the-treatment-of-relapsing-remitting-multiple-sclerosis
#10
Duygu Bozkaya, Terrie Livingston, Kristen Migliaccio-Walle, Tanner Odom
BACKGROUND: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs. AIMS: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US. MATERIALS AND METHODS: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e...
November 21, 2016: Journal of Medical Economics
https://www.readbyqxmd.com/read/27807435/glatiramer-acetate-dimethyl-fumarate-and-monomethyl-fumarate-upregulate-the-expression-of-ccr10-on-the-surface-of-natural-killer-cells-and-enhance-their-chemotaxis-and-cytotoxicity
#11
Azzam A Maghazachi, Kristin L Sand, Zaidoon Al-Jaderi
In vitro harnessing of immune cells is the most important advance in the field of cancer immunotherapy. Results shown in the current paper may be used to harness natural killer (NK) cells in vitro. It is observed that drugs used to treat multiple sclerosis such as glatiramer acetate, dimethyl fumarate, and monomethyl fumarate upregulate the expression of chemokines receptor 10 (CCR10) on the surface of human IL-2-activated NK cells. This is corroborated with increased chemotaxis of these cells toward the concentration gradients of the ligands for CCR10, namely CCL27 and CCL28...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27803638/disability-progression-after-switching-from-natalizumab-to-fingolimod-or-interferon-beta-glatiramer-acetate-therapies-a-narcoms-analysis
#12
Stacey S Cofield, Robert J Fox, Tuula Tyry, Amber R Salter, Denise Campagnolo
Background: Physicians must weigh the benefits against the risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab, especially beyond 2 years. However, disability progression associated with switching therapies versus continuing natalizumab therapy after 2 years has not been fully evaluated. Methods: In this retrospective analysis using the NARCOMS Registry, disability progression (Patient-Determined Disease Steps [PDDS] scale) and physical health-related quality of life (HRQOL) worsening (12-item Short Form Health Status Survey Physical Component Score [SF-12 PCS]) were compared between participants switching to fingolimod (n = 50) or interferon beta (IFNβ)/glatiramer acetate (GA) (n = 71) therapy and those continuing natalizumab (n = 406) after 2 years or more of treatment (median follow-up: natalizumab, 4 years; fingolimod, 4...
September 2016: International Journal of MS Care
https://www.readbyqxmd.com/read/27799134/management-of-immediate-hypersensitivity-reaction-to-glatiramer-acetate
#13
Emmanuelle Amsler, Jean Eric Autegarden, Hafida Gaouar, Camille Frances, Angele Soria
No abstract text is available yet for this article.
October 31, 2016: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/27798157/cd40-mediated-nf-%C3%AE%C2%BAb-activation-in-b-cells-is-increased-in-multiple-sclerosis-and-modulated-by-therapeutics
#14
Ding Chen, Sara J Ireland, Gina Remington, Enrique Alvarez, Michael K Racke, Benjamin Greenberg, Elliot M Frohman, Nancy L Monson
CD40 interacts with CD40L and plays an essential role in immune regulation and homeostasis. Recent research findings, however, support a pathogenic role of CD40 in a number of autoimmune diseases. We previously showed that memory B cells from relapsing-remitting multiple sclerosis (RRMS) patients exhibited enhanced proliferation with CD40 stimulation compared with healthy donors. In this study, we used a multiparameter phosflow approach to analyze the phosphorylation status of NF-κB and three major MAPKs (P38, ERK, and JNK), the essential components of signaling pathways downstream of CD40 engagement in B cells from MS patients...
October 26, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27785417/metabolic-response-to-glatiramer-acetate-therapy-in-multiple-sclerosis-patients
#15
Lidia De Riccardis, Alessandra Ferramosca, Antonio Danieli, Giorgio Trianni, Vincenzo Zara, Francesca De Robertis, Michele Maffia
Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4(+), the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27732670/type-ii-activation-of-macrophages-and-microglia-by-immune-complexes-enhances-th17-biasing-in-an-il-6-independent-manner
#16
Sarrabeth Stone, Anne Camille La Flamme
Macrophages can be activated into several distinct activation states. One of these states, type II activation, has a regulatory phenotype characterized by decreased IL-12 and increased IL-10, and has been shown to bias naïve CD4+ T cells to a Th2 response. Microglia, the resident macrophage-like cells in the central nervous system (CNS), are important contributors to neuroinflammation and, thus, we investigated if type II activated microglia could bias CD4+ T cell responses in a similar manner as type II activated macrophages...
2016: PloS One
https://www.readbyqxmd.com/read/27730845/peginterferon-beta-1a-versus-other-self-injectable-disease-modifying-therapies-in-the-treatment-of-relapsing-remitting-multiple-sclerosis-in-scotland-a-cost-effectiveness-analysis
#17
Luis Hernandez, Shien Guo, Hector Toro-Diaz, Stuart Carroll, Syed Feisal Syed Farooq
AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every two weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and personal social services perspective in Scotland...
October 12, 2016: Journal of Medical Economics
https://www.readbyqxmd.com/read/27721069/design-of-a-strong-cation-exchange-methodology-for-the-evaluation-of-charge-heterogeneity-in-glatiramer-acetate
#18
Víctor R Campos-García, Carlos A López-Morales, Eleuterio Benites-Zaragoza, Armando Jiménez-Miranda, Carlos E Espinosa-de la Garza, Daniel Herrera-Fernández, Jesús Padilla-Calderón, Néstor O Pérez, Luis F Flores-Ortiz, E Medina-Rivero
Complex pharmaceuticals are in demand of competent analytical methods able to analyze charge heterogeneity as a critical quality attribute (CQA), in compliance with current regulatory expectations. A notorious example is glatiramer acetate (GA), a complex polypeptide mixture useful for the treatment of relapsing-remitting multiple sclerosis. This pharmaceutical challenges the current state of analytical technology in terms of the capacity to study their constituent species. Thus, a strong cation exchange methodology was designed under the lifecycle approach to support the establishment of GA identity, trough the evaluation of its chromatographic profile, which acts as a charge heterogeneity fingerprint...
October 4, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27720845/identification-of-a-gene-expression-signature-in-peripheral-blood-of-multiple-sclerosis-patients-treated-with-disease-modifying-therapies
#19
Chiara Cordiglieri, Fulvio Baggi, Pia Bernasconi, Dimos Kapetis, Elisa Faggiani, Alessandra Consonni, Francesca Andreetta, Rita Frangiamore, Paolo Confalonieri, Carlo Antozzi, Renato Mantegazza
Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative alterations, ultimately progressing to neurological handicap. Therapies are effective in counteracting inflammation but not neurodegeneration. Biomarkers predicting disease course or treatment response are lacking. We investigated whether altered gene and protein expression profiles were detectable in the peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease-modifying therapies. A discovery/validation study on RR-MS responsive to glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3, CD177, IGJ, IL5RA, MMP8, P2RY12, and S100β...
October 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27704206/effect-of-teriflunomide-on-quantiferon-tb-gold-results
#20
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
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