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https://www.readbyqxmd.com/read/27910101/early-safety-and-efficacy-of-fingolimod-treatment-in-denmark
#1
A Voldsgaard, N Koch-Henriksen, M Magyari, F Sellebjerg, P S Sørensen, A B Oturai
BACKGROUND: Initiation of fingolimod treatment is associated with a transient decrease of heart rate, and atrioventricular (AV) conduction block may occur. OBJECTIVE: To evaluate the therapeutic effect and safety of fingolimod treatment in MS patients in Denmark with focus on cardiac and pulmonary side effects at treatment onset. MATERIALS & METHODS: We analysed data from the first 496 fingolimod-treated Danish patients, observed for at least 3 months...
January 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27907914/anxiety-and-coping-strategy-changes-in-multiple-sclerosis-patients-initiating-fingolimod-the-grace-prospective-study
#2
Thibault Moreau, Catherine Bungener, Olivier Heinzlef, Laurent Suchet, Florent Borgel, Isabelle Bourdeix, Mohamed Meite, Karin Rerat, Isabelle Chouette
The objective of this prospective study was to assess the changes in anxiety levels, and their relationship with coping strategies over the first four months of fingolimod treatment in patients with relapsing remitting multiple sclerosis (RRMS). Data were collected at the inclusion visit (Visit 1) and 4 months later (Visit 2). We used the Hospital Anxiety and Depression Scale (HADS) to assess the level of anxiety and the Coping Inventory for Stressful Situations scale to assess the coping strategies used when engaged with stressful situations...
December 2, 2016: European Neurology
https://www.readbyqxmd.com/read/27891572/safety-concerns-and-risk-management-of-multiple-sclerosis-therapies
#3
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/27890706/the-sphingosine-1-phosphate-receptor-a-novel-therapeutic-target-for-multiple-sclerosis-and-other-autoimmune-diseases
#4
REVIEW
Yang Mao-Draayer, Jeffrey Sarazin, David Fox, Elena Schiopu
Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous system (CNS). Currently, there is no drug that provides a cure for MS. To date, all immunotherapeutic drugs target relapsing remitting MS (RR-MS); it remains a daunting medical challenge in MS to develop therapy for secondary progressive MS (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P) receptor modulator FTY720 (fingolimod [Gilenya®]). for RR-MS in 2010, there have been many emerging studies with various selective S1P receptor modulators in other autoimmune conditions...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27888572/adverse-effect-profile-of-topical-ocular-administration-of-fingolimod-for-treatment-of-dry-eye-disease
#5
Weibao Xiao, Li Sun, Nan Zhang, Wen Ye
Fingolimod is a promising prodrug in attenuating multiple sclerosis and prolonging survival of organ allograft, with many other protective effects. Its mechanism of action is related to the internalization of sphingosine 1-phosphate receptors (S1PRs). Our previous study indicated that fingolimod eyedrop was efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of Non-Obese Diabetic (NOD) mice. In the current study, we evaluated potential adverse effects of fingolimod eyedrop. Inbred 10-week-old BALB/C mice were randomly divided into four groups, fingolimod-treated groups at three different concentrations (0...
November 26, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27886183/fingolimod-therapeutic-mechanisms-and-ocular-adverse-effects
#6
REVIEW
P Mandal, A Gupta, W Fusi-Rubiano, P A Keane, Y Yang
Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur...
November 25, 2016: Eye
https://www.readbyqxmd.com/read/27879549/fingolimod-use-for-the-treatment-of-multiple-sclerosis-in-a-clinical-practice-setting-in-madrid
#7
Victoria Galán Sánchez-Seco, Ignacio Casanova-Peño, Roberto Álvarez-Lafuente, Mónica Sánchez-Jiménez, Ángel García-Martínez, María Inmaculada Domínguez-Mozo, Ana María Arias-Leal, Marta García-Montojo, Rafael Arroyo-González
OBJECTIVE: To assess the effectiveness and safety of fingolimod use in a Spanish clinical practice setting. METHODS: Retrospective study with multiple sclerosis patients who received at least 1 fingolimod dose between January 2004 and January 2015. Effectiveness and safety data were collected during the entire treatment of each patient. Analysis was performed for the total population and stratified according to prior treatment, sex, and age at treatment initiation...
November 22, 2016: Clinical Neuropharmacology
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
#8
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/27857690/interferon-beta-increases-plasma-ceramides-of-specific-chain-length-in-multiple-sclerosis-patients-unlike-fingolimod-or-natalizumab
#9
Florian M Ottenlinger, Christoph A Mayer, Nerea Ferreirós, Yannick Schreiber, Anja Schwiebs, Katrin G Schmidt, Hanns Ackermann, Josef M Pfeilschifter, Heinfried H Radeke
Fingolimod is used for the treatment of multiple sclerosis (MS) and targets receptors for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Whether fingolimod or other MS therapies conversely affect plasma concentrations of sphingolipids has, however, not yet been analyzed. Herein, we quantified 15 representative sphingolipid species by mass spectrometry in plasma from relapsing-remitting MS patients currently under fingolimod (n = 24), natalizumab (n = 16), or IFN-β (n = 18) treatment. Healthy controls (n = 21) and untreated MS patients (n = 11) served as control groups...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27856777/virus-related-merkel-cell-carcinoma-complicating-fingolimod-treatment-for-multiple-sclerosis
#10
Heidi N Beadnall, Anthony J Gill, Sean Riminton, Michael H Barnett
No abstract text is available yet for this article.
November 16, 2016: Neurology
https://www.readbyqxmd.com/read/27853088/disseminated-cryptococcosis-in-a-63-year-old-patient-with-multiple-sclerosis-treated-with-fingolimod
#11
Hiroyuki Seto, Mitsushige Nishimura, Katsuhiro Minamiji, Sonoko Miyoshi, Hiroyuki Mori, Kenji Kanazawa, Hisafumi Yasuda
We herein report the case of a 63-year-old man who presented with a 3-month history of a cutaneous nodular lesion of his jaw, low grade fever, lethargy and progressive cognitive impairment. He had a 30-year history of multiple sclerosis and had been treated with fingolimod for the previous 2 years. Laboratory data revealed CD4 lymphocytopenia and a tissue culture of the skin nodule was positive for Cryptococcus neoformans. Cerebrospinal fluid and serum cryptococcal antigen tests were also positive and we diagnosed him to have disseminated cryptococcosis...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27829841/effects-of-fty720-fingolimod-on-proliferation-differentiation-and-migration-of-brain-derived-neural-stem-cells
#12
Botao Tan, Zeruxin Luo, Yan Yue, Yuan Liu, Li Pan, Lehua Yu, Ying Yin
Insufficient proliferation, differentiation, and migration are the main pitfalls of neural stem cells (NSCs) in reparative therapeutics for the central nervous system (CNS) diseases. The potent lipid mediator sphingosine-1-phosphate (S1P) regulates cells' biological behavior broadly in the CNS. However, the effects of activating S1P on NSCs are not quite clear. In the current study, FTY720 (Fingolimod), an analog of S1P, was employed to induce the proliferation, differentiation, and migration of cultured brain-derived NSCs...
2016: Stem Cells International
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
#13
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
#14
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/27827329/selective-sphingosine-1-phosphate-receptor-1-agonist-is-protective-against-ischemia-reperfusion-in-mice
#15
Vanessa H Brait, Gema Tarrasón, Amadeu Gavaldà, Núria Godessart, Anna M Planas
BACKGROUND AND PURPOSE: Growing evidence supports that the immunomodulatory drug fingolimod is protective in stroke. Fingolimod binds to 4 of 5 sphingosine-1-phosphate (S1P) receptors and, among other actions, it induces lymphopenia. In this study, we investigated whether a selective S1P1 agonist is protective in experimental stroke. METHODS: Drug selectivity was studied in vitro in cells overexpressing the human S1P receptors. Mice (n=54) received different doses of LASW1238 (3 or 10 mg/kg), fingolimod (1 mg/kg), or the vehicle intraperitoneal, and lymphopenia was studied at different time points...
November 8, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27825807/sphingosine-1-phosphate-receptor-therapies-advances-in-clinical-trials-for-cns-related-diseases
#16
REVIEW
Sinead O'Sullivan, Kumlesh K Dev
The family of sphingosine-1-phosphate receptors (S1PRs) are G protein-coupled and comprise of five subtypes, S1P1-S1P5. These receptors are activated by the sphingolipid ligand, S1P, which is produced from the phosphorylation of sphingosine by sphingosine kinases. The activation of S1PRs modulates a host of cellular processes such as cell proliferation, migration and survival. These receptors are targeted by the drug fingolimod, a first in class oral therapy for multiple sclerosis. Importantly, S1PRs have also been implicated, in cellular experiments, pre-clinical studies and clinical trials in a range of other neurodegenerative diseases, neurological disorders and psychiatric illnesses, where S1PR drugs are proving beneficial...
November 4, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27823573/the-sphingosine-1-phosphate-signaling-pathway-in-epilepsy-a-possible-role-for-the-immunomodulator-drug-fingolimod-in-epilepsy-treatment
#17
Antonio Leo, Rita Citraro, Rosario Marra, Ernesto Palma, Eugenio Donato Di Paola, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G protein-coupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis MS by preventing blood-brain barrier disruption and brain atrophy...
November 4, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27822961/the-cost-effectiveness-of-disease-modifying-therapies-for-the-treatment-of-relapsing-remitting-multiple-sclerosis
#18
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/27819760/reversible-cerebral-vasoconstriction-syndrome-in-association-with-fingolimod-use
#19
Scott Belliston, Jayshree Sundararajan, Kathy Newell, Sharon Lynch
BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is characterized by thunderclap headaches, non-aneurysmal segmental cerebral vasoconstriction seen on arteriogram, and spontaneously resolves within twelve weeks. Fingolimod has been reported to cause posterior reversible encephalopathy syndrome (PRES) and one case of RCVS. OBJECTIVE: We report a case of RCVS possibly related to fingolimod use, and compare to cases of adverse outcomes in fingolimod use...
November 7, 2016: International Journal of Neuroscience
https://www.readbyqxmd.com/read/27816167/inhibition-of-sphingosine-1-phosphate-receptors-in-ischemia-reperfusion-injured-autoimmunity-prone-mice
#20
Jess Edison, Sharon Frattalone, Christopher Tracy, Geoffrey E Woodard, Melissa Butts, C M Moratz
B6.MRL/lpr mice, an autoimmune strain, have an accelerated injury time course, increased intensity of tissue damage, and increased CD4+ T cell infiltration in the mesenteric ischemia/reperfusion injury model. In this study, the mechanism by which CD4+ T cells were recruited into injured tissue was addressed. Fingolimod (FTY720) was utilized to assess the role of infiltrating CD4+ T cells. FTY720 treatment was more effective in attenuating injury in B6.MRL/lpr mice then in control mice. Reduced CD4+ cell infiltration and tissue injury correlated with decreased neutrophil infiltration and pro-inflammatory cytokine generation...
October 27, 2016: Cellular Immunology
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