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https://www.readbyqxmd.com/read/28108364/from-natalizumab-to-fingolimod-in-eight-weeks-immunological-clinical-and-radiological-data-in-quest-of-the-optimal-switch
#1
Andrea Harrer, Georg Pilz, Katrin Oppermann, Marlene Sageder, Shahrzad Afazel, Elisabeth Haschke-Becher, Theo Rispens, Annick de Vries, Mark McCoy, Vlado Stevanovic, Wolfgang Hitzl, Eugen Trinka, Jörg Kraus, Johann Sellner, Peter Wipfler
Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28104252/novel-zebrafish-eae-model-a-quick-in-vivo-screen-for-multiple-sclerosis
#2
Pushkar Kulkarni, Swapna Yellanki, Raghavender Medishetti, Dharmarajan Sriram, Uday Saxena, Perumal Yogeeswari
INTRODUCTION: Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28104247/severe-rebound-after-withdrawal-of-fingolimod-treatment-in-patients-with-multiple-sclerosis
#3
Tuncay Gündüz, Murat Kürtüncü, Mefkure Eraksoy
No abstract text is available yet for this article.
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28101520/an-observational-study-of-alemtuzumab-following-fingolimod-for-multiple-sclerosis
#4
Mark Willis, Owen Pearson, Zsolt Illes, Tobias Sejbaek, Christian Nielsen, Martin Duddy, Kate Petheram, Caspar van Munster, Joep Killestein, Clas Malmeström, Emma Tallantyre, Neil Robertson
OBJECTIVE: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. METHODS: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers. RESULTS: Nine patients were identified...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28101047/acute-anterior-uveitis-in-a-patient-taking-fingolimod-fty720-for-multiple-sclerosis
#5
Heather Gwen Mack, Melissa Chih-Hui Tien, Owen Bruce White
Fingolimod is an oral sphingosine-1-phosphate (S1P) receptor modulator and the first oral therapy for relapsing-remitting multiple sclerosis. Its use has been complicated by a low rate of cystoid macular edema usually in the first 3 months after commencement of the medication. We report the case of a 34-year-old male with relapsing-remitting multiple sclerosis, who developed acute anterior uveitis on day 5 of fingolimod treatment. He responded to appropriate treatment and cessation of drug, but developed low-grade chronic anterior uveitis without cystoid macular edema...
September 2016: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/28100182/electrocardiographic-assessments-and-cardiac-events-after-fingolimod-first-dose-a-comprehensive-monitoring-study
#6
Volker Limmroth, Tjalf Ziemssen, Michael Lang, Stephan Richter, Bert Wagner, Judith Haas, Stephan Schmidt, Kathrin Gerbershagen, Christoph Lassek, Luisa Klotz, Olaf Hoffmann, Christian Albert, Katrin Schuh, Monika Baier-Ebert, Guillaume Wendt, Heinke Schieb, Susanne Hoyer, Ralf Dechend, Wilhelm Haverkamp
BACKGROUND: First dose observation for cardiac effects is required for fingolimod, but recommendations on the extent vary. This study aims to assess cardiac safety of fingolimod first dose. Individual bradyarrhythmic episodes were evaluated to assess the relevance of continuous electrocardiogram (ECG) monitoring. METHODS: START is an ongoing open-label, multi-center study. At the time of analysis 3951 patients were enrolled. The primary endpoints are the incidence of bradycardia (heart rate < 45 bpm) and second-/third-degree AV blocks during treatment initiation...
January 18, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28088313/q-space-myelin-map-imaging-for-longitudinal-analysis-of-demyelination-and-remyelination-in-multiple-sclerosis-patients-treated-with-fingolimod-a-preliminary-study
#7
Mariko Tanikawa, Jin Nakahara, Junichi Hata, Shigeaki Suzuki, Kanehiro Fujiyoshi, Hirokazu Fujiwara, Suketaka Momoshima, Masahiro Jinzaki, Masaya Nakamura, Hideyuki Okano, Shinichi Takahashi, Norihiro Suzuki
BACKGROUND: Fingolimod (FTY) is an oral sphingosine-1-phosphate receptor modulator that reduces relapse and slows brain atrophy in multiple sclerosis (MS) patients. In addition, FTY has been shown to enhance remyelination in certain animal models. OBJECTIVE: To analyze feasibility of a novel q-space Myelin Map imaging to monitor demyelination and remyelination under FTY treatment in MS patients. METHODS: Treatment outcomes of 24 consecutive MS patients treated with FTY were analyzed...
January 5, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28087821/selection-of-first-line-therapy-in-multiple-sclerosis-using-risk-benefit-decision-analysis
#8
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)...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28063629/the-autoimmune-risk-gene-zmiz1-is-a-vitamin-d-responsive-marker-of-a-molecular-phenotype-of-multiple-sclerosis
#9
N L Fewings, P N Gatt, F C McKay, G P Parnell, S D Schibeci, J Edwards, M A Basuki, A Goldinger, M J Fabis-Pedrini, A G Kermode, C P Manrique, J L McCauley, D Nickles, S E Baranzini, T Burke, S Vucic, G J Stewart, D R Booth
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS...
January 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28054340/fingolimod-confers-neuroprotection-through-activation-of-rac1-after-experimental-germinal-matrix-hemorrhage-in-rat-pups
#10
William B Rolland, Paul R Krafft, Tim Lekic, Damon Klebe, Julia LeGrand, Abby Jones Weldon, Liang Xu, John H Zhang
Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism of acute fingolimod-induced protection. GMH was induced in P7 rats by infusion of collagenase (0.3 U) into the right ganglionic eminence. Animals euthanized at four weeks post-GMH received low or high dose fingolimod (0...
January 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28043652/lymphocyte-subsets-as-biomarkers-of-therapeutic-response-in-fingolimod-treated-relapsing-multiple-sclerosis-patients
#11
D Paolicelli, A Manni, M D'Onghia, V Direnzo, P Iaffaldano, S Zoccolella, V Di Lecce, C Tortorella, G Specchia, M Trojano
We investigated, lymphocyte count (LC) and lymphocyte subpopulations (LS) in a real life setting of Fingolimod (FTY) treated Relapsing MS (RMS) patients. Peripheral blood counts with LS, relapses and MRI scans were recorded in a cohort of 119 FTY patients, during one year of treatment. Simple and multivariate logistic regression models, were performed. ROC analysis identified cut-off values of LS predicting a higher risk of relapses and of Gd+ lesions. We demonstrated a FTY-induced re-modulation of the immune system, suggesting that LS in RMS FTY treated patients can predict the clinical response to the drug...
December 21, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28035084/sphingosine-1-phosphate-receptor-modulators-and-drug-discovery
#12
REVIEW
Soo-Jin Park, Dong-Soon Im
Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P₁₋₅. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors...
January 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28008769/a-discrete-event-simulation-to-model-the-cost-utility-of-fingolimod-and-natalizumab-in-rapidly-evolving-severe-relapsing-remitting-multiple-sclerosis-in-the-uk
#13
Stephen Montgomery, Maciej Maruszczak, David Slater, Jeanette Kusel, Richard Nicholas, Nicholas Adlard
OBJECTIVE: Two disease modifying therapies are licensed in the EU for use in rapidly-evolving severe (RES) relapsing-remitting multiple sclerosis (RRMS), fingolimod and natalizumab. Here a discrete event simulation (DES) model to analyse the cost-effectiveness of natalizumab and fingolimod in the RES population, from the perspective of the National Health Service (NHS) in the UK, is reported. METHODS: A DES model was developed to track individual RES patients, based on Expanded Disability Status Scale scores...
December 23, 2016: Journal of Medical Economics
https://www.readbyqxmd.com/read/28008201/active-brain-changes-after-initiating-fingolimod-therapy-in-multiple-sclerosis-patients-using-individual-voxel-based-analyses-for-diffusion-tensor-imaging
#14
Joe Senda, Hirohisa Watanabe, Kuniyuki Endo, Keizo Yasui, Yasuhiro Hawsegawa, Noritaka Yoneyama, Takashi Tsuboi, Kazuhiro Hara, Mizuki Ito, Naoki Atsuta, Bagarinao Epifanio, Masahisa Katsuno, Shinji Naganawa, Gen Sobue
Voxel-based analysis (VBA) of diffusion tensor images (DTI) and voxel-based morphometry (VBM) in patients with multiple sclerosis (MS) can sensitively detect occult tissue damage that underlies pathological changes in the brain. In the present study, both at the start of fingolimod and post-four months clinical remission, we assessed four patients with MS who were evaluated with VBA of DTI, VBM, and fluid-attenuated inversion recovery (FLAIR). DTI images for all four patients showed widespread areas of increased mean diffusivity (MD) and decreased fractional anisotropy (FA) that were beyond the high-intensity signal areas across images...
December 2016: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28007551/a-preliminary-investigation-of-phoshodiesterase-7-inhibitor-vp3-15-as-therapeutic-agent-for-the-treatment-of-experimental-autoimmune-encephalomyelitis-mice
#15
R Martín-Álvarez, N Paúl-Fernández, V Palomo, C Gil, A Martínez, G Mengod
cAMP plays a significant role in signal transduction pathways controlling multiple cellular processes such as inflammation and immune regulation. cAMP levels are regulated by a family of phosphodiesterases (PDEs). We have studied the effects of a novel PDE7 inhibitor (PDE7i) treatment on mice with experimental autoimmune encephalomyelitis (EAE) a model of multiple sclerosis (MS) and compared it with another PDE7i. EAE was induced by immunizing C57BL/6J mice with myelin oligodendrocyte glycoprotein (MOG35-55) peptide...
December 19, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28003234/fingolimod-gilenya-and-melanoma
#16
Christopher Lee Robinson, Mary Guo
The Food and Drug Administration (FDA) had approved fingolimod usage for multiple sclerosis in 2010. Melanoma after the usage of fingolimod immunomodulation was reported rarely in clinical trials, and only two case reports exist in the published literature, both occurring in Europe. Most of the incidences reported in clinical trials were in-situ, whereas both case reports were of malignant melanoma. Fingolimod has been found to inhibit metastatic melanoma growth in a mouse model that depends on vascular endothelial growth factor (VEGF)-induced angiogenesis for metastasis...
December 21, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27999525/antidepressant-drug-treatment-in-association-with-multiple-sclerosis-disease-modifying-therapy-using-explorys-in-the-ms-population
#17
Matthew M Mirsky, Ruth Ann Marrie, Alexander Rae-Grant
Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population...
November 2016: International Journal of MS Care
https://www.readbyqxmd.com/read/27994897/progressive-multifocal-leukoencephalopathy-in-a-multiple-sclerosis-patient-diagnosed-after-switching-from-natalizumab-to-fingolimod
#18
Tim Sinnecker, Jalal Othman, Marc Kühl, Imke Metz, Thoralf Niendorf, Annett Kunkel, Friedemann Paul, Jens Wuerfel, Juergen Faiss
Background. Natalizumab- (NTZ-) associated progressive multifocal leukoencephalopathy (PML) is a severe and often disabling infectious central nervous system disease that can become evident in multiple sclerosis (MS) patients after NTZ discontinuation. Recently, novel diagnostic biomarkers for the assessment of PML risk in NTZ treated MS patients such as the anti-JC virus antibody index have been reported, and the clinical relevance of milky-way lesions detectable by MRI has been discussed. Case Presentation and Conclusion...
2016: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/27983657/fingolimod-associated-bilateral-cystoid-macular-edema-wait-and-see
#19
REVIEW
Refik Pul, Alma Osmanovic, Holger Schmalstieg, Amelie Pielen, Kaweh Pars, Philipp Schwenkenbecher, Kurt Wolfram Sühs, Özlem Yildiz, Benedikt Frank, Martin Stangel, Thomas Skripuletz
Fingolimod 0.5-mg once-daily is an approved therapy for patients with relapsing-remitting multiple sclerosis (MS). Several pivotal and real-world studies have demonstrated that fingolimod is associated with the development of macular edema (ME). Herein, we present a case of a diabetic MS patient who developed severe bilateral ME during fingolimod treatment. By means of this case study we provide a detailed review about fingolimod associated macular edema (FAME), its current incidence with or without diabetes mellitus, and previous therapy attempts and outcomes in MS patients...
December 14, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27976804/a-longitudinal-real-life-comparison-study-of-natalizumab-and-fingolimod
#20
R Lanzillo, A Carotenuto, M Moccia, F Saccà, C V Russo, M Massarelli, A De Rosa, V Brescia Morra
BACKGROUND: Different retrospective studies compared natalizumab and fingolimod in relapsing-remitting multiple sclerosis (RRMS), with conflicting results. We aimed to explore the prescriptive attitude and the clinical outcome of the two therapies. METHODS: We retrospectively included all RRMS patients treated with natalizumab (n=101) or fingolimod (n=78) as their first second-line therapy with at least 24-month follow-up. Demographic and clinical features were recorded to calculate the propensity score (PS)...
December 15, 2016: Acta Neurologica Scandinavica
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