Randomized Trial of Oral Teriflunomide for Relapsing Multiple Sclerosis

University of Toronto, Toronto, ON, Canada.
New England Journal of Medicine (Impact Factor: 55.87). 10/2011; 365(14):1293-303. DOI: 10.1056/NEJMoa1014656
Source: PubMed

ABSTRACT Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis.
We concluded a randomized trial involving 1088 patients with multiple sclerosis, 18 to 55 years of age, with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years. Patients were randomly assigned (in a 1:1:1 ratio) to placebo, 7 mg of teriflunomide, or 14 mg of teriflunomide once daily for 108 weeks. The primary end point was the annualized relapse rate, and the key secondary end point was confirmed progression of disability for at least 12 weeks.
Teriflunomide reduced the annualized relapse rate (0.54 for placebo vs. 0.37 for teriflunomide at either 7 or 14 mg), with relative risk reductions of 31.2% and 31.5%, respectively (P<0.001 for both comparisons with placebo). The proportion of patients with confirmed disability progression was 27.3% with placebo, 21.7% with teriflunomide at 7 mg (P=0.08), and 20.2% with teriflunomide at 14 mg (P=0.03). Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging (MRI). Diarrhea, nausea, and hair thinning were more common with teriflunomide than with placebo. The incidence of elevated alanine aminotransferase levels (≥1 times the upper limit of the normal range) was higher with teriflunomide at 7 mg and 14 mg (54.0% and 57.3%, respectively) than with placebo (35.9%); the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group (6.3%, 6.7%, and 6.7%, respectively). Serious infections were reported in 1.6%, 2.5%, and 2.2% of patients in the three groups, respectively. No deaths occurred.
Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. (Funded by Sanofi-Aventis; TEMSO number, NCT00134563.).

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Available from: Jerry S Wolinsky, Dec 18, 2013
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    • "Teriflunomide is pregnancy category X [43]. Elevation in liver transaminases is a common side effect for all of these agents including FAEs [42] [44] [45] [46]. When taking patient compliance into consideration, oral drugs are preferred over injectable ones. "
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    ABSTRACT: Autoimmune diseases are the diseases of the modern century. Due to their complicated pathogenesis and the enrollment of many factors in disease initiation and progression, these diseases are considered uneasy to treat. Immune cells exist normally in our bodies. They are extremely essential for our survival against many pathogenic and foreign particles. Manipulating these cells through chemical and biological drugs has tremendous effects, usually with risks outweighing the benefits, as a result of the disturbance of cellular defense mechanisms. This chapter is devoted to the description of two different autoimmune diseases; multiple sclerosis (MS) and psoriasis. Up to date there is no known cure for MS and psoriasis. The available treatments approved by the FDA are mainly considered symptom relieving drugs and their major therapeutic action is only to slow the disease progression, and they lack the ability to eliminate the disease completely. A great devotion in this chapter was given to discuss several aspects regarding fumarate acid esters (FAEs) including; pharmacokinetics, mode of action, recommendations and specifically their potential as an effective treatment for psoriasis and MS.
    Commonly Used Drugs - Uses, Side Effects, Bioavailability & Approaches to Improve it, 1 edited by Rafik Karaman, 01/2015: chapter 8: pages 249-261; Nova Science Publishers., ISBN: 978-1-63463-828-9
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    • "[46] "
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    ABSTRACT: Drugs (medicines) are considered either the primary therapy or an adjunct to another modality. Physicians of all specialties prescribe drugs on a daily basis, and therefore they need to understand the mode and action by which drugs exert their therapeutic effects. Written records of the use of natural products as medicinal agents date back thousands of years. However, it was not until the early 1800s that the active principles from plants were isolated. Since then thousands of drugs have been introduced to the drugs market. With advances in drug design, molecular biology and genetics, the rate of developing new potent drugs is accelerated. Due to the vast progress in drug development and discovery, medical and pharmacy students, doctors, nurses and pharmacists in training need to learn the principles of therapeutics in order to follow up with the frequent changes in the therapeutics and adapt to them. With contributions from some of my colleagues, this book provides a clear and concise overview of the most important commonly used drugs with emphasis on the pharmacology aspects necessary for a basic understanding of the subject. It reviews the concepts, clinical applications, dosage forms, bioavailability, pharmacokinetics and side effects of a large number of drugs used to alleviate pain, lower cholesterol levels, and treat bacterial infections, diabetes, osteoporosis, bleeding, psoriasis and multiple Sclerosis. This book, with over 750 references, is an excellent pharmacology text for the student who is looking to broaden his/her strengths prior to the exam. The beauty of this text is that it includes essential pharmacology concepts in a compact book that can be quickly referenced and read multiple times during the course of a student's studies. In addition, this guide assists scientists trained in molecular biology, medicinal chemistry and related fields who need to know the basic theories, principles and practical applications of pharmacology. With the addition of pharmacokinetics coverage, ways to improve the bioavailability of commonly used drugs and sections on therapeutics that will help readers identify with diseases and drug treatments, this book provides better preparation of researchers in the basics of pharmacology.
    1 edited by Rafik Karaman, 01/2015; Nova Science Publishers, Inc., NY, USA., ISBN: 9781634638289
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    • "However, it should be noted that linomide was associated with unexpected serious AEs in a study of patients with RRMS or SPMS, having been previously well tolerated in other indications [59]. While clinical trials have shown that teriflunomide reduced relapses and delayed disability progression compared with placebo [60, 61], a head-to-head study versus IFN beta-1a SC (TENERE; #NCT00883337) has also shown no superiority of daily teriflunomide versus high-frequency IFN in patients with MS [62]. "
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    ABSTRACT: Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and intravenous alemtuzumab] indicated for first-line use in relapsing–remitting MS. Here we review the clinical trial and follow-up data for IFN beta-1b and discuss factors that clinicians may consider when selecting this treatment, both at first line in early MS, and later in the disease course. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0149-1) contains supplementary material, which is available to authorized users.
    Advances in Therapy 09/2014; 31(9). DOI:10.1007/s12325-014-0149-1 · 2.27 Impact Factor
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