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https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#1
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
#2
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 13, 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
#3
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
#4
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
#5
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
#6
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
#7
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...
January 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28155573/oral-contraceptives-and-ms-disease-activity-in-a-contemporary-real-world-cohort
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28090798/switching-from-branded-to-generic-glatiramer-acetate-15-month-gate-trial-extension-results
#14
Krzysztof Selmaj, Frederik Barkhof, Anna N Belova, Christian Wolf, Evelyn Rw van den Tweel, Janine Jl Oberyé, Roel Mulder, David F Egging, Norbert P Koper, Jeffrey A Cohen
BACKGROUND: Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone(®) (GATE) trial. OBJECTIVE: To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment. METHODS: A total of 729 patients received GTR 20 mg/mL daily...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28087821/selection-of-first-line-therapy-in-multiple-sclerosis-using-risk-benefit-decision-analysis
#15
David Bargiela, Matthew T Bianchi, M Brandon Westover, Lori B Chibnik, Brian C Healy, Philip L De Jager, Zongqi Xia
OBJECTIVE: To integrate long-term measures of disease-modifying drug efficacy and risk to guide selection of first-line treatment of multiple sclerosis. METHODS: We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving natalizumab (NTZ), fingolimod (FGL), or glatiramer acetate (GA) over 30 years. Leveraging publicly available data, we integrated treatment utility, disability worsening, and risk of PML into quality-adjusted life-years (QALYs)...
February 14, 2017: Neurology
https://www.readbyqxmd.com/read/28081190/inflammatory-activity-on-natalizumab-predicts-short-term-but-not-long-term-disability-in-multiple-sclerosis
#16
Joel Raffel, Arie R Gafson, Samer Dahdaleh, Omar Malik, Brynmor Jones, Richard Nicholas
BACKGROUND: In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis. OBJECTIVE: To study this association in those receiving natalizumab. METHODS: Data were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability...
2017: PloS One
https://www.readbyqxmd.com/read/28077493/disease-modifying-therapies-modulate-retinal-atrophy-in-multiple-sclerosis-a-retrospective-study
#17
Julia Button, Omar Al-Louzi, Andrew Lang, Pavan Bhargava, Scott D Newsome, Teresa Frohman, Laura J Balcer, Elliot M Frohman, Jerry Prince, Peter A Calabresi, Shiv Saidha
OBJECTIVE: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT). METHODS: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up...
February 7, 2017: Neurology
https://www.readbyqxmd.com/read/28064019/the-random-co-polymer-glatiramer-acetate-rapidly-kills-primary-human-leukocytes-through-sialic-acid-dependent-cell-membrane-damage
#18
Stig Hill Christiansen, Xianwei Zhang, Kristian Juul-Madsen, Michael Lykke Hvam, Brian Stougaard Vad, Manja Annette Behrens, Ida Lysgaard Thygesen, Babak Jalilian, Jan Skov Pedersen, Kenneth A Howard, Daniel E Otzen, Thomas Vorup-Jensen
The formulation glatiramer acetate (GA) is widely used in therapy of multiple sclerosis. GA consists of random copolymers of four amino acids, in ratios that produce a predominantly positive charge and an amphipathic character. With the extraordinary complexity of the drug, several pharmacological modes-of-action were suggested, but so far none, which rationalizes the cationicity and amphipathicity as part of the mode-of-action. Here, we report that GA rapidly kills primary human T lymphocytes and, less actively, monocytes...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28063616/chitinase-3-like-1-is-associated-with-the-response-to-interferon-beta-treatment-in-multiple-sclerosis
#19
Clara Matute-Blanch, Jordi Río, Luisa M Villar, Luciana Midaglia, Sunny Malhotra, José C Álvarez-Cermeño, Angela Vidal-Jordana, Xavier Montalban, Manuel Comabella
Chitinase 3-like 1 (CHI3L1) plays a prognostic role in patients with multiple sclerosis (MS). Here, we investigated a potential association between CHI3L1 and the response to interferon-beta (IFNβ) and glatiramer acetate (GA). Serum CHI3L1 levels were measured by ELISA in 117 relapsing-remitting MS (RRMS) patients, 76 IFNβ-treated and 41 GA-treated patients. CHI3L1 levels were increased by GA (p=0.014) but unchanged by IFNβ (p=0.830). CHI3L1 was associated with IFNβ response and levels were higher in non-responder group (p=0...
December 18, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28052269/observational-study-of-switching-from-natalizumab-to-immunomodulatory-drugs
#20
Ramón Villaverde-González, Julia Gracia Gil, Angel Pérez Sempere, Jorge Millán Pascual, José Marín Marín, María Carcelén Gadea, Laura Gabaldón Torres, Antonio Moreno Escribano, Antonio Candeliere Merlicco
OBJECTIVE: To determine the effect of disease-modifying drugs (DMDs) on disease activity rebound in patients discontinuing natalizumab (NTZ). METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis (RRMS) treated with NTZ for ≥1 year and who switched to DMDs (glatiramer acetate [GA] or interferon) were followed up for 12 months in clinical practice. Clinical outcomes after NTZ cessation were assessed every 3 months for 1 year and MRI was performed at 12 months...
January 5, 2017: European Neurology
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