Journal ArticleDOI
Pathophysiology of multiple sclerosis and the place of teriflunomide
Ralf Gold,Jerry S. Wolinsky +1 more
Reads0
Chats0
TLDR
Gold R, Wolinsky JS.Abstract:
Significant progress in multiple sclerosis (MS) treatment has been made over the last two decades, including the emergence of disease-modifying therapy (DMT). However, substantial unmet medical need persists and has stimulated the search for new therapeutics. Teriflunomide, one of the several oral DMTs under investigation, is a selective inhibitor of de novo pyrimidine synthesis which exerts a cytostatic effect on proliferating T- and B lymphocytes in the periphery and thus has both antiproliferative and anti-inflammatory properties. Anti-inflammatory effects have been demonstrated in rodent MS models, with reductions in macrophage and B- and T-cell infiltration in the central nervous system and preservation of myelin and oligodendrocytes. Delays in disease onset, reductions in disease relapses and improvements in clinical symptoms were also observed. A proof-of-concept clinical trial in patients with relapsing MS demonstrated that teriflunomide significantly reduced magnetic resonance imaging (MRI) activity and improved clinical endpoints, with both effects maintained with longer-term treatment. Additional studies have shown that teriflunomide can be safely added to beta interferon or glatiramer acetate therapy, with some evidence of additional improvements in MRI disease burden and clinical signs. Teriflunomide has an acceptable and manageable safety and tolerability profile. A large clinical programme is underway to further elucidate the role of teriflunomide in the treatment of MS.read more
Citations
More filters
Journal ArticleDOI
Randomized Trial of Oral Teriflunomide for Relapsing Multiple Sclerosis
Paul O'Connor,Jerry S. Wolinsky,Christian Confavreux,Giancarlo Comi,Ludwig Kappos,Tomas Olsson,Hadj Benzerdjeb,Philippe Truffinet,Lin Wang,Aaron E. Miller,Mark S. Freedman +10 more
TL;DR: Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo.
Journal Article
Multiple Sclerosis Review
TL;DR: Multiple sclerosis (MS) typically presents in adults 20 to 45 years of age; occasionally, it presents in childhood or late middle age.
Journal ArticleDOI
Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial.
Christian Confavreux,Paul O'Connor,Giancarlo Comi,Mark S. Freedman,Aaron E. Miller,Tomas Olsson,Jerry S. Wolinsky,Teresa Bagulho,Jean Luc Delhay,Deborah Dukovic,Philippe Truffinet,Ludwig Kappos +11 more
TL;DR: Teriflunomide 14 mg was associated with a lower relapse rate and less disability accumulation compared with placebo, with a similar safety and tolerability profile to that reported in previous studies.
Journal ArticleDOI
Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy
TL;DR: S1P signaling effects relevant to MS in neural cell types expressing S1P receptors, including astrocytes, oligodendrocyte, neurons, microglia and dendritic cells are reviewed.
Journal ArticleDOI
Teriflunomide and Its Mechanism of Action in Multiple Sclerosis
TL;DR: Results from animal experiments modelling the immune activation implicated in MS demonstrate reductions in disease symptoms with teriflunomide treatment, accompanied by reduced central nervous system lymphocyte infiltration, reduced axonal loss, and preserved neurological functioning, demonstrating how terifnomide acts as a selective immune therapy for patients with MS.
References
More filters
Journal ArticleDOI
Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria
Chris H. Polman,Stephen C. Reingold,Brenda Banwell,Michel Clanet,Jeffrey A. Cohen,Massimo Filippi,Kazuo Fujihara,Eva Havrdova,Michael Hutchinson,Ludwig Kappos,Fred D. Lublin,Xavier Montalban,Paul L. O’Connor,Magnhild Sandberg-Wollheim,Alan J. Thompson,Emmanuelle Waubant,Brian G. Weinshenker,Jerry S. Wolinsky +17 more
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Journal ArticleDOI
Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".
Chris H. Polman,Stephen C. Reingold,Gilles Edan,Massimo Filippi,Hans-Peter Hartung,Ludwig Kappos,Fred D. Lublin,Luanne M. Metz,Henry F. McFarland,Paul O'Connor,Magnhild Sandberg-Wollheim,Alan J. Thompson,Brian G. Weinshenker,Jerry S. Wolinsky +13 more
TL;DR: New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease.
Journal ArticleDOI
Axonal transection in the lesions of multiple sclerosis.
TL;DR: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
Journal ArticleDOI
Defining the clinical course of multiple sclerosis Results of an international survey
TL;DR: An international survey of clinicians involved with MS revealed areas of consensus about some terms classically used to describe types of the disease and other areas for which there was lack of consensus and proposed standardized definitions for the most common clinical courses of patients with MS.
Journal ArticleDOI
Multiple Sclerosis — The Plaque and Its Pathogenesis
TL;DR: This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque.