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Teriflunomide

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https://www.readbyqxmd.com/read/29050250/teriflunomide-restores-5-azacytidine-sensitivity-via-activation-of-pyrimidine-salvage-in-5-azacytidine-resistant-leukemia-cells
#1
Satoshi Imanishi, Ryoko Takahashi, Seiichiro Katagiri, Chiaki Kobayashi, Tomohiro Umezu, Kazuma Ohyashiki, Junko H Ohyashiki
Previous studies showed that downregulation of pyrimidine salvage underlies resistance against 5-azacytidine (AZA), indicating an important role for de novo pyrimidine synthesis in AZA resistance. Because de novo pyrimidine synthesis is inhibited by the immunomodulator teriflunomide and its pro-drug leflunomide, we examined the effect of combined treatment with AZA and teriflunomide on AZA resistance to develop a novel strategy to cancel and prevent AZA resistance. Teriflunomide markedly inhibited the growth of AZA-resistant human leukemia cell lines (R-U937 and R-HL-60) in comparison with their AZA-sensitive counterparts (U937 and HL-60)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29038464/unveiling-some-fda-approved-drugs-as-inhibitors-of-the-store-operated-ca-2-entry-pathway
#2
Saifur Rahman, Taufiq Rahman
The store-operated calcium entry (SOCE) pathway is an important route for generating cytosolic Ca(2+) signals that regulate a diverse array of biological processes. Abnormal SOCE seem to underlie several diseases that notably include allergy, inflammation and cancer. Therefore, any modulator of this pathway is likely to have significant impact in cell biology under both normal and abnormal conditions. In this study, we screened the FDA-approved drug library for agents that share significant similarity in 3D shape and surface electrostatics with few, hitherto best known inhibitors of SOCE...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28913785/evolution-of-patient-reported-outcomes-and-their-role-in-multiple-sclerosis-clinical-trials
#3
REVIEW
Cindy J Nowinski, Deborah M Miller, David Cella
Patient-reported outcomes (PROs) are playing an increasing role in multiple sclerosis (MS) research and practice, and are essential for understanding the effects that MS and MS treatments have on patients' lives. PROs are captured directly from patients and include symptoms, function, health status, and health-related quality of life. In this article, we review different categories (e.g., generic, targeted, preference-based) of PRO measures and considerations in selecting a measure. The PROs included in MS clinical research have evolved over time, as have the measures used to assess them...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28913765/treatment-of-theiler-s-virus-induced-demyelinating-disease-with-teriflunomide
#4
Francesca Gilli, Libin Li, Darlene B Royce, Krista D DiSano, Andrew R Pachner
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28878732/multiple-sclerosis-treatments-affect-monocyte-derived-microvesicle-production
#5
Maria Blonda, Antonella Amoruso, Roberta Grasso, Valeria Di Francescantonio, Carlo Avolio
Microvesicles (MVs) are released by immune cells especially of the myeloid lineage upon stimulation with ATP on its cognate receptor P2X7, both in physiological and pathological conditions. In multiple sclerosis (MS) the role of MVs remains little investigated. We aimed to compare the release of MVs in peripheral blood monocytes from MS patients with healthy donors (HDs) and to see how current MS treatment may affect such a production. We also assessed the treatment effect on M1 and M2 monocyte polarization and on the inflammasome components...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28831550/persistence-to-oral-disease-modifying-therapies-in-multiple-sclerosis-patients
#6
Simona Lattanzi, Maura Danni, Ruja Taffi, Raffaella Cerqua, Giulia Carlini, Alessandra Pulcini, Leandro Provinciali, Mauro Silvestrini
Dimethyl fumarate (DMF), fingolimod (FTY) and teriflunomide (TFN) are oral disease-modifying therapies (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS) whose efficacy and tolerability have been separately assessed in phase III trials. Conversely, little evidence exists about their head-to-head comparison. The aim of the study was to evaluate the 1-year persistence to DMF, FTY and TFN in patients with RRMS. Patients affected by RRMS who started treatment with DMF, FTY or TFN were identified...
August 22, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28828394/teriflunomide-slows-bvl-in-relapsing-ms-a-reanalysis-of-the-temso-mri-data-set-using-siena
#7
Ernst-Wilhelm Radue, Till Sprenger, Laura Gaetano, Nicole Mueller-Lenke, Steve Cavalier, Karthinathan Thangavelu, Michael A Panzara, Jessica E Donaldson, Fiona M Woodward, Jens Wuerfel, Jerry S Wolinsky, Ludwig Kappos
OBJECTIVE: To assess, using structural image evaluation using normalization of atrophy (SIENA), the effect of teriflunomide, a once-daily oral immunomodulator, on brain volume loss (BVL) in patients with relapsing forms of MS enrolled in the phase 3 TEMSO study. METHODS: TEMSO MR scans were analyzed (study personnel masked to treatment allocation) using SIENA to assess brain volume changes between baseline and years 1 and 2 in patients treated with placebo or teriflunomide...
September 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28814828/comparison-of-efficacy-and-safety-of-oral-agents-for-the-treatment-of-relapsing-remitting-multiple-sclerosis
#8
REVIEW
Cristina Guarnera, Placido Bramanti, Emanuela Mazzon
In the therapeutic scenario of disease-modifying therapies for relapsing-remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing-remitting multiple sclerosis, are reviewed in this work. Results of Phase III clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate - a superior efficacy compared to placebo...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28796815/effect-of-teriflunomide-on-cortex-basal-ganglia-thalamus-cxbgth-circuit-glutamatergic-dysregulation-in-the-theiler-s-murine-encephalomyelitis-virus-mouse-model-of-multiple-sclerosis
#9
Claire M Modica, Ferdinand Schweser, Michelle L Sudyn, Nicola Bertolino, Marilena Preda, Paul Polak, Danielle M Siebert, Jacqueline C Krawiecki, Michele Sveinsson, Jesper Hagemeier, Michael G Dwyer, Suyog Pol, Robert Zivadinov
BACKGROUND: Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors. OBJECTIVES: To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler's Murine Encephalomyelitis Virus, (TMEV) mouse model of MS...
2017: PloS One
https://www.readbyqxmd.com/read/28737986/real-world-adherence-and-persistence-to-oral-disease-modifying-therapies-in-multiple-sclerosis-patients-over-1-year
#10
Kristen M Johnson, Huanxue Zhou, Feng Lin, John J Ko, Vivian Herrera
BACKGROUND: Disease-modifying therapies (DMTs) are indicated to reduce relapse rates and slow disease progression for relapsing-remitting multiple sclerosis (MS) patients when taken as prescribed. Nonadherence or non-persistence in the real-world setting can lead to greater risk for negative clinical outcomes. Although previous research has demonstrated greater adherence and persistence to oral DMTs compared with injectable DMTs, comparisons among oral DMTs are lacking. OBJECTIVE: To compare adherence, persistence, and time to discontinuation among MS patients newly prescribed the oral DMTs fingolimod, dimethyl fumarate, or teriflunomide...
August 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28732355/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#11
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28686222/multiple-sclerosis-immunopathology-and-treatment-update
#12
REVIEW
Narges Dargahi, Maria Katsara, Theodore Tselios, Maria-Eleni Androutsou, Maximilian de Courten, John Matsoukas, Vasso Apostolopoulos
The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year...
July 7, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28680917/predicting-long-term-disability-outcomes-in-patients-with-ms-treated-with-teriflunomide-in-temso
#13
Maria Pia Sormani, Philippe Truffinet, Karthinathan Thangavelu, Pascal Rufi, Catherine Simonson, Nicola De Stefano
OBJECTIVE: To predict long-term disability outcomes in TEMSO core (NCT00134563) and extension (NCT00803049) studies in patients with relapsing forms of MS treated with teriflunomide. METHODS: A post hoc analysis was conducted in a subgroup of patients who received teriflunomide in the core study, had MRI and clinical relapse assessments at months 12 (n = 552) and 18, and entered the extension. Patients were allocated risk scores for disability worsening (DW) after 1 year of teriflunomide treatment: 0 = low risk; 1 = intermediate risk; and 2-3 = high risk, based on the occurrence of relapses (0 to ≥2) and/or active (new and enlarging) T2-weighted (T2w) lesions (≤3 or >3) after the 1-year MRI...
September 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28574826/leflunomide-teriflunomide-inhibit-epstein-barr-virus-ebv-induced-lymphoproliferative-disease-and-lytic-viral-replication
#14
Andrea Bilger, Julie Plowshay, Shidong Ma, Dhananjay Nawandar, Elizabeth A Barlow, James C Romero-Masters, Jillian A Bristol, Zhe Li, Ming-Han Tsai, Henri-Jacques Delecluse, Shannon C Kenney
EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#15
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
August 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28506594/fingolimod-and-teriflunomide-attenuate-neurodegeneration-in-mouse-models-of-neuronal-ceroid-lipofuscinosis
#16
Janos Groh, Kristina Berve, Rudolf Martini
CLN diseases are rare lysosomal storage diseases characterized by progressive axonal degeneration and neuron loss in the CNS, manifesting in disability, blindness, and premature death. We have previously demonstrated that, in animal models of infantile and juvenile forms of CLN disease (CLN1 and CLN3, respectively), secondary neuroinflammation in the CNS substantially amplifies neural damage, opening the possibility that immunomodulatory treatment might improve disease outcome. First, we recapitulated the inflammatory phenotype, originally seen in mice in autopsies of CLN patients...
August 2, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28440858/treatment-with-disease-modifying-drugs-for-people-with-a-first-clinical-attack-suggestive-of-multiple-sclerosis
#17
REVIEW
Graziella Filippini, Cinzia Del Giovane, Marinella Clerico, Omid Beiki, Miriam Mattoscio, Federico Piazza, Sten Fredrikson, Irene Tramacere, Antonio Scalfari, Georgia Salanti
BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28396093/what-s-new-about-oral-treatments-in-multiple-sclerosis-immunogenetics-still-under-question
#18
REVIEW
Cristiana Pistono, Cecilia Osera, Chiara Boiocchi, Giulia Mallucci, Mariaclara Cuccia, Roberto Bergamaschi, Alessia Pascale
Multiple Sclerosis (MS) is a chronic pathology affecting the Central Nervous System characterized by inflammatory processes that lead to demyelination and neurodegeneration. In MS treatment, disease modifying therapies (DMTs) are essential to reduce disease progression by suppressing the inflammatory response responsible for promoting lesion formation. Recently, in addition to the classical injectable DMTs like Interferons and Glatiramer acetate, new orally administered drugs have been approved for MS therapy: dimethyl fumarate, teriflunomide and fingolimod...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28321835/teriflunomide-for-multiple-sclerosis-in-real-world-setting
#19
M L Elkjaer, T Molnar, Z Illes
OBJECTIVES: Teriflunomide 14 mg is a once-daily oral disease-modifying treatment for relapsing-remitting multiple sclerosis. We examined adverse event (AE) profile and efficacy in real life. MATERIALS AND METHODS: In this observational cohort study, we retrospectively examined 1521 blood samples and data of 102 patients followed for up to 28 months. RESULTS: The number of female patients starting teriflunomide peaked in the fifth decade, 10 years later compared to male patients (P<...
March 20, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28304217/the-efficacy-of-teriflunomide-in-patients-who-received-prior-disease-modifying-treatments-subgroup-analyses-of-the-teriflunomide-phase-3-temso-and-tower-studies
#20
Mark S Freedman, Jerry S Wolinsky, Giancarlo Comi, Ludwig Kappos, Tomas P Olsson, Aaron E Miller, Karthinathan Thangavelu, Myriam Benamor, Philippe Truffinet, Paul W O'Connor
Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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