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Teriflunomide

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https://www.readbyqxmd.com/read/29627017/effect-of-teriflunomide-on-gray-and-white-matter-brain-pathology-in-multiple-sclerosis-using-volumetric-and-diffusion-tensor-imaging-mri-measures
#1
Robert Zivadinov, Niels Bergsland, Jesper Hagemeier, Ellen Carl, Hanna Kolb, David Hojnacki, Bianca Weinstock-Guttman
OBJECTIVES: To investigate the effect of teriflunomide on microstructural pathology in the gray matter (GM) and white matter (WM), as measured by changes in brain volume and diffusion-tensor imaging (DTI) in patients with multiple sclerosis (MS). METHODS: 30 relapsing MS patients and 20 healthy controls (HCs) were enrolled in the study and followed prospectively for 12 months with clinical and 3T MRI examinations. Of those, 26 MS patients and 18 HCs completed the 6-month and 22 MS and 16 HCs patients the 12-month follow-up...
May 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29621808/in-vitro-human-dihydroorotate-dehydrogenase-inhibitory-anti-inflammatory-and-cytotoxic-activities-of-alkaloids-from-the-seeds-of-nigella-glandulifera
#2
Jun-Bo Gao, Xing-Jie Zhang, Rui-Han Zhang, Li-Li Zhu, De-Bing Pu, Xiao-Li Li, Hong-Lin Li, Min Xu, Wei-Lie Xiao
Four new dolabellane-type diterpene alkaloids, glandulamines A - D (1:  - 4: ), together with twelve known compounds (5:  - 16: ), were isolated from the seeds of Nigella glandulifera using repeated column chromatography and semipreparative HPLC. The structures of 1:  - 16: were elucidated based on NMR data analysis, HRMS experiments and other spectroscopic interpretations. The absolute configuration of 5: was determined by single-crystal X-ray diffraction data for the first time. Compounds 10: and 12: showed human dihydroorotate dehydrogenase inhibitory activity with IC50 values of 61...
April 5, 2018: Planta Medica
https://www.readbyqxmd.com/read/29600441/efficacy-and-safety-of-the-newer-multiple-sclerosis-drugs-approved-since-2010
#3
REVIEW
Simon Faissner, Ralf Gold
Multiple sclerosis treatment faces tremendous changes as a result of the approval of new medications. The new medications have differing safety considerations and risks after long-term treatment, which are important for treating physicians to optimize and individualize multiple sclerosis care. Since the approval of the first multiple sclerosis capsule, fingolimod, the armamentarium of multiple sclerosis therapy has grown with the orally available medications dimethyl fumarate and teriflunomide. Fingolimod is mainly associated with cardiac side effects, dimethyl fumarate with bowel symptoms...
March 29, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29534752/teriflunomide-promotes-oligodendroglial-differentiation-and-myelination
#4
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29530550/fingolimod-inhibits-brain-atrophy-and-promotes-brain-derived-neurotrophic-factor-in-an-animal-model-of-multiple-sclerosis
#5
Paul A Smith, Cindy Schmid, Stefan Zurbruegg, Magali Jivkov, Arno Doelemeyer, Diethilde Theil, Valérie Dubost, Nicolau Beckmann
Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain...
March 3, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29526118/first-line-disease-modifying-drugs-in-relapsing-remitting-multiple-sclerosis-an-italian-real-life-multicenter-study-on-persistence
#6
Diana Ferraro, Valentina Camera, Eleonora Baldi, Veria Vacchiano, Erica Curti, Angelica Guareschi, Susanna Malagù, Sara Montepietra, Silvia Strumia, Mario Santangelo, Luisa Caniatti, Matteo Foschi, Alessandra Lugaresi, Franco Granella, Ilaria Pesci, Luisa Motti, Walter Neri, Paolo Immovilli, Enrico Montanari, Francesca Vitetta, Anna Maria Simone, Patrizia Sola
OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for Relapsing-Remitting Multiple Sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. Aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months...
March 10, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29500302/oral-therapies-for-multiple-sclerosis
#7
Simon Faissner, Ralf Gold
Multiple sclerosis treatment faces tremendous changes owing to the approval of new medications, some of which are available as oral formulations. Until now, the four orally available medications, fingolimod, dimethylfumarate (BG-12), teriflunomide, and cladribine have received market authorization, whereas laquinimod is still under development. Fingolimod is a sphingosine-1-phosphate inhibitor, which is typically used as escalation therapy and leads to up to 60% reduction of the annualized relapse rate, but might also have neuroprotective properties...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29473796/severe-hypertriglyceridemia-associated-with-teriflunomide-in-a-patient-with-multiple-sclerosis-a-case-report
#8
Carlos R Camara-Lemarroy, Joaquín Castilló, Jaume Sastre-Garriga, Mar Tintore, Xavier Montalban
OBJECTIVE: To describe a case of severe hypertriglyceridemia in a patient receiving teriflunomide. METHODS: This is a case study. RESULTS: Our patient developed severe hypertriglyceridemia (>5000 mg/dL) while on teriflunomide. The drug was withdrawn. Resolution began over 3 weeks later. CONCLUSION: We describe the first probable case of teriflunomide-associated severe hypertriglyceridemia in a patient with multiple sclerosis, an adverse event previously associated with leflunomide in patients with rheumatologic diseases...
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29473795/clinical-commentary-on-severe-hypertriglyceridemia-associated-with-teriflunomide-in-a-patient-with-multiple-sclerosis
#9
Simon Faissner, Ralf Gold
No abstract text is available yet for this article.
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29464673/comparison-of-disease-modifying-therapies-for-the-management-of-multiple-sclerosis-analysis-of-healthcare-resource-utilization-and-relapse-rates-from-us-insurance-claims-data
#10
Jacqueline Nicholas, Aaron Boster, Ning Wu, Wei-Shi Yeh, Monica Fay, Jon Kendter, Ming-Yi Huang, Andrew Lee
BACKGROUND: Data on comparative healthcare resource utilization and costs associated with the newer oral disease-modifying therapies (DMTs) for managing relapsing-remitting multiple sclerosis (MS) in routine clinical practice are limited. The purpose of this study was to estimate healthcare resource utilization, costs, and relapse rates in the year after initiating treatment with dimethyl fumarate (DMF), interferon (IFN)-β, glatiramer acetate (GA), teriflunomide, or fingolimod in routine clinical practice for patients with MS who did not receive a DMT in the previous year...
March 2018: PharmacoEconomics open
https://www.readbyqxmd.com/read/29429031/the-changing-multiple-sclerosis-treatment-landscape-impact-of-new-drugs-and-treatment-recommendations
#11
Irene Eriksson, Joris Komen, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used). METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017...
February 10, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29427785/mitochondrial-dysfunction-induced-by-leflunomide-and-its-active-metabolite
#12
Jiekun Xuan, Zhen Ren, Tao Qing, Letha Couch, Leming Shi, William H Tolleson, Lei Guo
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29336841/economic-impact-of-the-new-oral-treatments-for-multiple-sclerosis
#13
L Álvarez Ayuso, B Rodríguez Marrodán, M R Blasco Quílez, J A García-Merino, A Sánchez Guerrero
INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda...
January 11, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29229891/cost-effectiveness-of-oral-agents-in-relapsing-remitting-multiple-sclerosis-compared-to-interferon-based-therapy-in-saudi-arabia
#14
Mai F Alsaqa'aby, Varun Vaidya, Noura Khreis, Thamer Al Khairallah, Ahmed H Al-Jedai
BACKGROUND: Promising clinical and humanistic outcomes are associated with the use of new oral agents in the treatment of relapsing-remitting multiple sclerosis (RRMS). This is the first cost-effectiveness study comparing these medications in Saudi Arabia. OBJECTIVES: We aimed to compare the cost-effectiveness of fingolimod, teriflunomide, dimethyl fumarate, and interferon (IFN)-b1a products (Avonex and Rebif) as first-line therapies in the treatment of patients with RRMS from a Saudi payer perspective...
November 2017: Annals of Saudi Medicine
https://www.readbyqxmd.com/read/29221122/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#15
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...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212829/pml-in-a-person-with-multiple-sclerosis-is-teriflunomide-the-felon
#16
Lorena Lorefice, Giuseppe Fenu, Simonetta Gerevini, Jessica Frau, Giancarlo Coghe, Maria Antonietta Barracciu, Franco Contu, Maria Giovanna Marrosu, Eleonora Cocco
No abstract text is available yet for this article.
January 9, 2018: Neurology
https://www.readbyqxmd.com/read/29204190/oral-teriflunomide-in-the-treatment-of-relapsing-forms-of-multiple-sclerosis-clinical-evidence-and-long-term-experience
#17
REVIEW
Aaron E Miller
Key objectives in the treatment of multiple sclerosis (MS) include prevention of relapses, a reduction in the accumulation of disability and slowing of the brain volume loss that occurs from the earliest stages of the disease. Teriflunomide, a once-daily, oral immunomodulatory therapy, has demonstrated efficacy across multiple measures of disease activity and worsening in patients with relapsing forms of MS and in those with a first clinical episode suggestive of MS. In this review, the latest evidence relating to the proposed mechanism of action of teriflunomide in MS is explored, including novel insights provided from the recently completed Teri-DYNAMIC study...
December 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29141803/-nail-loss-after-teriflunomide-treatment-a-new-potential-adverse-event
#18
L Mancinelli, P Amerio, M di Ioia, V Di Tommaso, G De Luca, M Onofrj, A Lugaresi
Nail loss might represent a new, reversible, adverse event associated with teriflunomide treatment. It shares close analogies with hair loss and thinning, known adverse events of teriflunomide. MS specialists should be aware of this possibility and evaluate treatment discontinuation.
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29082295/teriflunomide-treatment-reduces-b-cells-in-patients-with-ms
#19
Ilaria Gandoglia, Federico Ivaldi, Alice Laroni, Federica Benvenuto, Claudio Solaro, Gianluigi Mancardi, Nicole Kerlero de Rosbo, Antonio Uccelli
OBJECTIVE: To study the immunomodulatory effect of teriflunomide on innate and adaptive immune cell populations through a pilot, open-label, observational study in a cohort of patients with relapsing-remitting MS. METHODS: Blood lymphocytes were isolated from 10 patients with MS before and after 3 or 12 months of treatment. Adaptive and innate immune cell subsets were analyzed by flow cytometry as follows: B cells (memory, regulatory, and mature subsets), T cells (effector and regulatory subsets), and natural killer (NK) cells (CD56dim and CD56bright subsets)...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29064296/tolerability-and-efficacy-of-colestipol-hydrochloride-for-accelerated-elimination-of-teriflunomide
#20
COMPARATIVE STUDY
Derrick Robertson, Crystal Dixon, Angela Aungst, Bradlee McCoy, Natalie Moreo, Lise Casady, Janice Maldonado
BACKGROUND: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended...
December 2017: Expert Review of Clinical Pharmacology
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