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https://www.readbyqxmd.com/read/28328179/effect-of-delayed-release-dimethyl-fumarate-on-no-evidence-of-disease-activity-in-relapsing-remitting-multiple-sclerosis-integrated-analysis-of-the-phase-iii-define-and-confirm-studies
#1
E Havrdova, G Giovannoni, R Gold, R J Fox, L Kappos, J Theodore Phillips, M Okwuokenye, J L Marantz
BACKGROUND AND PURPOSE: Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years...
March 22, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28319417/alterations-in-serum-levels-of-il-17-in-contrast-to-tnf-alpha-correspond-to-disease-modifying-treatment-in-relapsing-remitting-multiple-sclerosis
#2
Anastasiya Georgieva Trenova, Georgi Svetoslavov Slavov, Maria Georgieva Manova, Milena Nenkova Draganaova-Filipova, Nonka Georgieva Mateva, Lyuba Dineva Miteva, Spaska Angelova Stanilova
Cytokines of different types play an important role in multiple sclerosis (MS) pathogenesis as mediators and regulators of the immune processes in the central nervous system. The aim of the study was to determine the effect of interferon-beta and glatiramer acetate on serum concentrations of TNF-alpha and IL-17 A and their correlation with the degree of disability in clinically stable patients with relapsing-remitting MS. A cross-sectional, case-control study of 220 patients (68 treatment naïve; 152 treated with interferon-beta or glatiramer acetate) and 99 clinically healthy age-gender-body mass index-matched subjects were performed...
March 20, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28292329/glatiramer-acetate-treatment-persistence-but-not-adherence-in-multiple-sclerosis-patients-is-predicted-by-health-related-quality-of-life-and-self-efficacy-a-prospective-web-based-patient-centred-study-cair-study
#3
Peter Joseph Jongen, Wim A Lemmens, Erwin L Hoogervorst, Rogier Donders
BACKGROUND: In patients with relapsing remitting multiple sclerosis (RRMS) the persistence of and adherence to disease modifying drug (DMD) treatment is inadequate. To take individualised measures there is a need to identify patients with a high risk of non-persistence or non-adherence. As patient-related factors have a major influence on persistence and adherence, we investigated whether health-related quality of life (HRQoL) and self-efficacy could predict persistence or adherence. METHODS: In a prospective web-based patient-centred study in 203 RRMS patients, starting treatment with glatiramer acatete (GA) 20 mg subcutaneously daily, we measured physical and mental HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire), functional and control self-efficacy (Multiple Sclerosis Self-Efficacy Scale), the 12-month persistence rate and, in persistent patients, the percentage of missed doses...
March 14, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28273762/natural-killer-cell-subpopulations-are-associated-with-mri-activity-in-a-relapsing-remitting-multiple-sclerosis-patient-cohort-from-australia
#4
P Caruana, K Lemmert, K Ribbons, R Lea, J Lechner-Scott
BACKGROUND: The importance of the innate immune system in multiple sclerosis (MS) is increasingly recognized and the role of natural killer (NK) cells in controlling autoimmunity may be an important modulator of disease activity. OBJECTIVE: To examine NK subsets in MS patients on different treatments and to evaluate the role of NK subsets as indicators for disease activity. METHODS: We measured NK subset levels in blood obtained from 110 relapsing-remitting MS patients...
November 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28254244/a-potential-life-threatening-reaction-to-glatiramer-acetate-in-rett-syndrome
#5
Andreea Nissenkorn, Mona Kidon, Bruria Ben-Zeev
BACKGROUND: Rett syndrome is an X-linked dominant neurodevelopmental disorder manifesting with severe intellectual disability in females caused by various mutations in the MECP2 gene. Brain-derived neurotrophic factor (BDNF) is one of the main proteins regulated by the MECP2 protein; its overexpression in the MeCP2 mouse model partially corrects the Rett phenotype. Pharmacologic manipulations that lead to increased BDNF in individuals with Rett syndrome are expected to have a positive effect on the disorder...
March 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28240190/demonstration-of-biological-and-immunological-equivalence-of-a-generic-glatiramer-acetate
#6
Josephine D D Alessandro, Kevin Garofalo, Ganlin Zhao, Christopher Honan, Jay Duffner, Ishan Capila, Ian Fier, Ganesh Kaundinya, Daniel Kantor, Tanmoy Ganguly
In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone. In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, antigen-presenting cell biology, T-cell biology, and B-cell biology) modulated by glatiramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#7
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#8
REVIEW
Marianne von Euler Chelpin, Thomas Vorup-Jensen
Parkinson's Disease (PD) is the second most common neurodegenerative disease in the world, however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
February 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28212923/multiple-sclerosis-in-the-real-world-a-systematic-review-of-fingolimod-as-a-case-study
#9
REVIEW
Tjalf Ziemssen, Jennie Medin, C Anne-Marie Couto, Catherine R Mitchell
INTRODUCTION: The aim of our study was to systematically review the growing body of published literature reporting on one specific multiple sclerosis (MS) treatment, fingolimod, in the real world to assess its effectiveness in patients with MS, evaluate methodologies used to investigate MS in clinical practice, and describe the evidence gaps for MS as exemplified by fingolimod. METHODS: We conducted a PRISMA-compliant systematic review of the literature (cut-off date: 4 March 2016)...
February 15, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28211024/comparative-effectiveness-research-of-disease-modifying-therapies-for-the-management-of-multiple-sclerosis-analysis-of-a-large-health-insurance-claims-database
#10
Aaron Boster, Jacqueline Nicholas, Ning Wu, Wei-Shi Yeh, Monica Fay, Michael Edwards, Ming-Yi Huang, Andrew Lee
INTRODUCTION: Limited data are available on the real-world effectiveness of newer oral disease-modifying therapies (DMTs) in multiple sclerosis. The purpose of this study was to retrospectively compare the real-world effectiveness of dimethyl fumarate (DMF), fingolimod, teriflunomide, and injectable DMTs in routine clinical practice based on US claims data. METHODS: Patients newly-initiating DMF, interferon beta (IFNβ), glatiramer acetate (GA), teriflunomide, or fingolimod in 2013 were identified in the Truven MarketScan Commercial Claims Databases (N = 6372)...
February 16, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28210662/time-course-of-glatiramer-acetate-efficacy-in-patients-with-rrms-in-the-gala-study
#11
Mat D Davis, Natalia Ashtamker, Joshua R Steinerman, Volker Knappertz
OBJECTIVE: To determine the time to efficacy onset of glatiramer acetate (GA) 40 mg/mL 3-times-weekly formulation (GA40). METHODS: This post hoc analysis of data from the 1-year, double-blind, placebo-controlled phase of the Glatiramer Acetate Low-Frequency Administration study (NCT01067521) of GA40 in patients with relapsing-remitting MS (RRMS) sought to determine the timing of efficacy onset using a novel data-censoring approach. RESULTS: Compared with placebo-treated patients, those receiving GA40 exhibited a >30% reduction in the accumulated annualized relapse rate (ARR) within 2 months of initiating treatment and generally sustained this treatment difference during the 1-year study...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28209373/cost-utility-of-first-line-disease-modifying-treatments-for-relapsing-remitting-multiple-sclerosis
#12
Erkki Soini, Jaana Joutseno, Marja-Liisa Sumelahti
PURPOSE: This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. METHODS: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting)...
February 13, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28188020/efficacy-of-immunomodulatory-therapy-with-interferon-%C3%AE-or-glatiramer-acetate-on-multiple-sclerosis-associated-uveitis
#13
D Velazquez-Villoria, C Macia-Badia, A Segura-García, S Pastor Idoate, G Arcos-Algaba, L Velez-Escola, J García-Arumí
AIM: To analyse the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. METHOD: A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis...
February 7, 2017: Archivos de la Sociedad Española de Oftalmología
https://www.readbyqxmd.com/read/28161400/memory-b-cells-are-major-targets-for-effective-immunotherapy-in-relapsing-multiple-sclerosis
#14
REVIEW
David Baker, Monica Marta, Gareth Pryce, Gavin Giovannoni, Klaus Schmierer
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28155573/oral-contraceptives-and-ms-disease-activity-in-a-contemporary-real-world-cohort
#15
Riley Bove, Kelsey Rankin, Alicia S Chua, Taylor Saraceno, Neda Sattarnezhad, Emily Greeke, Fiona Stuart, Allison LaRussa, Bonnie I Glanz, Tanuja Chitnis
BACKGROUND: There is uncertainty regarding the effect of oral hormonal contraceptives (OC) on multiple sclerosis (MS) course. OBJECTIVE: To evaluate the hypothesis that OC use is associated with decreased risk of relapses in an observational study of women of childbearing age with new-onset MS starting a first-line injectable disease-modifying therapy (DMT). METHODS: From our CLIMB longitudinal observational study, we identified 162 women with MS or CIS with known OC use who initiated injectable DMT within two years of symptom onset, and categorized OC use at DMT onset as past, ever or never...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28130412/update-on-disease-modifying-therapies-for-multiple-sclerosis
#16
Diana L Vargas, William R Tyor
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women and is one of the most common causes of disability in young adults. MS is characterized by formation of white matter lesions in the CNS as a result of inflammation, demyelination, and axonal loss. Treatment has been a focus of neurological research for over 60 years. A number of disease-modifying therapies (DMTs) have become available making MS a treatable disease. These compounds target the inflammatory response in MS...
January 27, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28109694/sirt1-as-a-potential-biomarker-of-response-to-treatment-with-glatiramer-acetate-in-multiple-sclerosis
#17
Daniel Hewes, Alexandru Tatomir, Adam M Kruszewski, Gautam Rao, Cosmin A Tegla, Jonathan Ciriello, Vingh Nguyen, Walter Royal, Christopher Bever, Violeta Rus, Horea Rus
SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses...
January 19, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28104259/utility-of-extension-views-in-spondylotic-myelopathy-mimicking-transverse-myelitis
#18
Brittani L Conway, Michelle J Clarke, Timothy J Kaufmann, Eoin P Flanagan
Cervical spondylotic myelopathy is a common cause of myelopathy and may mimic transverse myelitis. We report a 55 year-old lady with subacute myelopathy initially treated with glatiramer acetate for suspected clinically isolated syndrome. MRI head and spine revealed a single short cervical cord T2-hyperintense lesion with enhancement just below a region of moderate stenosis. Cerebrospinal fluid revealed elevated oligoclonal bands. Repeat MRI 7 months later showed persistent enhancement. Dynamic MRI revealed cord compression during extension...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28094337/glatiramer-acetate-attenuates-the-activation-of-cd4-t-cells-by-modulating-stat1-and-3-signaling-in-glia
#19
Ye-Hyeon Ahn, Sae-Bom Jeon, Chi Young Chang, Eun-Ah Goh, Sang Soo Kim, Ho Jin Kim, Jaewhan Song, Eun Jung Park
Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and -3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and -3 by MS-associated stimuli such as IFNγ or LPS in primary glia, but not neurons...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093681/quantifying-the-benefits-of-dimethyl-fumarate-over-%C3%AE-interferon-and-glatiramer-acetate-therapies-on-work-productivity-outcomes-in-ms-patients
#20
Andrew Lee, James Pike, Michael R Edwards, Jennifer Petrillo, John Waller, Eddie Jones
INTRODUCTION: Dimethyl fumarate (DMF) is a novel oral therapy used for the treatment of relapse-remitting multiple sclerosis (RRMS). In two 2-year pivotal Phase 3 trials in patients with RRMS, DMF significantly reduced disease activity based on both clinical and magnetic resonance imaging (MRI) findings and demonstrated an acceptable safety profile. However, there is currently a lack of comparative data which explore the relationship between work productivity and health-related quality of life (HRQoL) outcomes in RRMS and how these differ among RRMS therapies, including DMF...
January 16, 2017: Neurology and Therapy
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