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Jens Zierle, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: Teriflunomide, an inhibitor of pyrimidine synthesis and thus proliferation of activated T and B lymphocytes, is successfully used for treatment of inflammatory disease. Teriflunomide has further been shown to trigger apoptosis of tumor cells and has thus been considered for the treatment of malignancy. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and phospholipid scrambling of the cell membrane with translocation of phosphatidylserine to the erythrocyte surface...
October 24, 2016: Cellular Physiology and Biochemistry
Javier Ochoa-Repáraz, Sara L Colpitts, Christopher Kircher, Eli J Kasper, Kiel M Telesford, Sakhina Begum-Haque, Anudeep Pant, Lloyd H Kasper
OBJECTIVE: To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally. METHODS: C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
André Duquette, Anne Julie Frenette, Maxime Doré
OBJECTIVE: To report the case of a patient treated with leflunomide that presented with chronic diarrhea associated with high teriflunomide blood concentration. An 84-year-old woman taking leflunomide 20 mg once daily for the past 2 years to treat rheumatoid arthritis (RA) was investigated for severe chronic diarrhea that had been worsening for the past 5 months. The patient's general condition progressively deteriorated and included electrolyte imbalances and a transient loss of consciousness...
June 2016: Rheumatol Ther
Ashley M Hopkins, Mahin Moghaddami, David Jr Foster, Susanna M Proudman, Richard N Upton, Michael D Wiese
Leflunomide's active metabolite teriflunomide inhibits dihydro-oroate dehydrogenase (DHODH), an enzyme essential to proliferation of T-lymphocytes. As teriflunomide must reach the target site to have this effect, this study assessed the distribution of teriflunomide into T-lymphocytes, as intracellular concentrations may be a superior response biomarker to plasma concentrations. CD3 MicroBeads (MiltenyiBiotec) were used to extract CD3(+) T-cells from the peripheral blood of patients with rheumatoid arthritis whom were taking a stable dose of leflunomide...
October 14, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
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No abstract text is available yet for this article.
October 4, 2016: Neurology
Saskia M Leibowitz, Jun Yan
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways are involved in cell immune responses, apoptosis and infections. In multiple sclerosis (MS), NF-κB pathways are changed, leading to increased levels of NF-κB activation in cells. This may indicate a key role for NF-κB in MS pathogenesis. NF-κB signaling is complex, with many elements involved in its activation and regulation. Interestingly, current MS treatments are found to be directly or indirectly linked to NF-κB pathways and act to adjust the innate and adaptive immune system in patients...
2016: Frontiers in Molecular Neuroscience
Tara Nazareth, Howard S Friedman, Prakash Navaratnam, Denise A Herriott, John J Ko, Peri Barr, Rahul Sasane
BACKGROUND: In the US, the approved multiple sclerosis (MS) oral disease-modifying therapies (ODMTs) are fingolimod (FTY), teriflunomide (TFN), and dimethyl fumarate (DMF). FTY and TFN are recommended with once-daily doses with no up-titration, whereas DMF treatment is recommended twice-daily (BID) and is initiated with a 7-day starter dose of 120 mg BID before up-titration to the maintenance dose of 240 mg BID. Limited information exists regarding real-world ODMT prescribing patterns to aid physician/patient decision-making...
September 29, 2016: BMC Neurology
Tanja Wostradowski, Chittappen Kandiyil Prajeeth, Viktoria Gudi, Jessica Kronenberg, Sina Witte, Marina Brieskorn, Martin Stangel
BACKGROUND: Teriflunomide, an inhibitor of dihydroorotate dehydrogenase, is thought to ameliorate multiple sclerosis by reducing activation-induced proliferation of lymphocytes, which is highly dependent on de novo pyrimidine synthesis. Nevertheless, its immunomodulatory effects on resident glial cells in the central nervous system are only poorly understood. METHODS: In this study, we employed physiologically relevant concentrations of teriflunomide and investigated its effects on survival, proliferation, activation, and function of primary rat microglia in vitro...
2016: Journal of Neuroinflammation
Emer Fogarty, Susanne Schmitz, Niall Tubridy, Cathal Walsh, Michael Barry
INTRODUCTION: Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. METHODS: A systematic review identified 28 randomised, placebo-controlled and direct comparative trials...
September 2016: Multiple Sclerosis and related Disorders
Jasna Jancic, Blazo Nikolic, Nikola Ivancevic, Vesna Djuric, Ivan Zaletel, Dejan Stevanovic, Sasa Peric, John N van den Anker, Janko Samardzic
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment...
September 17, 2016: Neurology and Therapy
Diogo Mendes, Carlos Alves, Francisco Batel-Marques
OBJECTIVE: This study aimed to test the number needed to treat to benefit (NNTB) and to harm (NNTH), and the likelihood to be helped or harmed (LHH) when assessing benefits, risks, and benefit-risk ratios of disease-modifying treatments (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS). METHODS: In May 2016, we conducted a systematic review using the PubMed and Cochrane Central Register of Controlled Trials databases to identify phase III, randomized controlled trials with a duration of ≥2 years that assessed first-line (dimethyl fumarate [DMF], glatiramer acetate [GA], β-interferons [IFN], and teriflunomide) or second-line (alemtuzumab, fingolimod, and natalizumab) DMTs in patients with RRMS...
October 2016: CNS Drugs
Min Xu, Xuesheng Lu, Jing Fang, Xiaoqi Zhu, Jie Wang
The aim of this study was to evaluate the efficacy and safety of teriflunomide in reducing the frequency of relapses and progression of physical disability in patients with relapsing multiple sclerosis (RMS). Literatures were searched in Pubmed, Medline and Embase to screen citations from January 1990 to April 2015. Studies of parallel group design comparing teriflunomide and placebo for RMS were screened. After independent review of 234 citations by two authors, seven studies were identified as meeting the inclusion criteria...
November 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Patrick Vermersch, Jeremy Hobart, Catherine Dive-Pouletty, Sylvie Bozzi, Steven Hass, Patricia K Coyle
BACKGROUND: The Treatment Satisfaction Questionnaire for Medication (TSQM) was designed to assess patient treatment satisfaction in chronic diseases. Its performance has not been examined in multiple sclerosis (MS). The 14 items of the TSQM cover four domains: Effectiveness, Side Effects, Convenience, and Global Satisfaction. OBJECTIVE: To evaluate performance of the TSQM in patients with relapsing MS, using data collected from the TENERE study (NCT00883337), in which 324 patients received oral teriflunomide or subcutaneous interferon beta-1a for ⩾48 weeks...
June 30, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Marta Simone, Tanuja Chitnis
Pediatric multiple sclerosis (PedMS) is a rare disease with a more severe prognosis compared to adult-onset MS. It remains a challenging condition to treat because of the highly inflammatory nature of the disease, the prominent cognitive issues, and the limited knowledge about the efficacy and safety of current available disease-modifying therapies. Over the past decade, there has been a dramatic increase in the number of drugs licensed for adult-onset MS and several of them, although not tested in PedMS, are currently being used off-label in this population...
August 2016: Current Treatment Options in Neurology
Martin Diebold, Tobias Derfuss
Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs...
April 2016: Seminars in Hematology
David E Jones
PURPOSE OF REVIEW: This article provides an evidence-based approach to the management of patients with early relapsing multiple sclerosis (MS). RECENT FINDINGS: Numerous clinical trials have shown the role of disease-modifying therapies in reducing relapses and new MRI lesions in patients with relapsing MS. Many of these trials also show the ability of these agents to delay disability progression, and a few suggest that disease-modifying therapies may slow brain atrophy in relapsing MS; however, very few suggest that disease-modifying therapies can improve symptoms or disability...
August 2016: Continuum: Lifelong Learning in Neurology
Mathias Mäurer, Giancarlo Comi, Mark S Freedman, Ludwig Kappos, Tomas P Olsson, Jerry S Wolinsky, Aaron E Miller, Catherine Dive-Pouletty, Sylvie Bozzi, Paul W O'Connor
BACKGROUND: Two pivotal phase 3 teriflunomide studies provided data on relapses, fatigue, and health-related quality of life (HRQoL) in patients with relapsing forms of multiple sclerosis (MS). OBJECTIVES: Using pooled data from the TEMSO (NCT00134563) and TOWER (NCT00751881) studies, we investigated the association between relapse severity, and changes from baseline to Week 108 in fatigue and HRQoL outcomes. METHODS: Four definitions of relapse severity were applied in this analysis: sequelae post-relapse; relapse leading to hospitalization; relapse requiring intravenous corticosteroids; and intense relapse...
May 2016: Multiple Sclerosis and related Disorders
Hongbo Yi, Denghu Jiang, Lin Zhang, Haitao Xiong, Feifei Han, Yizhen Wang
The signal transducer and activator of transcription (STAT) proteins play essential roles in apoptosis, proliferation and survival. However, the role of STATs in intestinal inflammation during weaning is unclear. This study aimed to investigate developmental expression of STATs, nuclear factor-κB (NF-κB) and inflammatory genes in the jejunum of piglets during weaning. Thirty-two piglets were weaned at 21d and sacrificed at 0, 1, 7, or 14d (n=8) after weaning. Villus height and the villus height/crypt depth ratio were decreased, whereas crypt depth was increased in the jejunum at 7 and 14d after weaning...
May 6, 2016: International Immunopharmacology
Mitra Habibi, Huda-Marie Kuttab
PURPOSE: The management of multiple sclerosis (MS) and the integration of related specialty pharmacy programs within health systems are discussed. SUMMARY: MS is a progressive immune-mediated inflammatory disease of the central nervous system. Current treatment strategies include the use of disease-modifying therapies (DMTs) that have various degrees of efficacy and tolerability. These DMTs also differ with respect to frequency and route of administration, which can significantly impact patient compliance and ultimately their response to therapy...
June 1, 2016: American Journal of Health-system Pharmacy: AJHP
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