Drug Healthc Patient Saf. 2013;5:37-47. doi: 10.2147/DHPS.S28822. Epub 2013 Feb 26.
Oral available agents in the treatment of relapsing remitting multiple sclerosis: an overview of merits and culprits.
Drug, healthcare and patient safety
Jan Thöne, Gisa Ellrichmann
Affiliations
Affiliations
- Department of Neurology, St JosefHospital Bochum, Ruhr-University Bochum, Bochum, Germany.
PMID: 23459383
PMCID: PMC3585507 DOI: 10.2147/DHPS.S28822
Abstract
Multiple sclerosis (MS) is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Major therapeutic progress has occurred during the past decade, in particular since the introduction of immunomodulatory agents, however, MS is still an incurable disease. In addition, parenteral application of the currently licensed drugs is associated with injection-related adverse events (AEs) and low patient compliance. Thus, there remains an unmet need for the development of more effective and well tolerated oral therapies for the treatment of MS. A number of new orally administered agents including fingolimod, laquinimod, teriflunomide, cladribine, and BG-12 have been licensed recently or are currently under investigation in relapsing remitting MS patients. In multi-center, randomized, placebo-controlled phase III clinical studies, all of these agents have already shown their efficacy on both clinical disease parameters and magnetic resonance imaging-based measures of disease activity in patients with relapsing remitting MS. However, there are essential differences concerning their clinical efficacy and side-effect profiles. Additionally, the mechanisms by which these substances exert clinical efficacy have not been fully elucidated. In this article, we review the pharmaceutical properties of fingolimod, laquinimod, teriflunomide, cladribine, and BG-12; and their suggested mechanisms of action, clinical efficacy, and side-effect profiles.
Keywords: cladribine; fingolimod (FTY); fumaric acid esters (BG-12); laquinimod; teriflunomide
References
- Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):365-70 - PubMed
- J Neurol. 2010 Feb;257(2):163-70 - PubMed
- Mult Scler. 2010 Nov;16(11):1360-6 - PubMed
- Lancet Neurol. 2012 May;11(5):420-8 - PubMed
- J Neuroimmunol. 2006 Apr;173(1-2):69-78 - PubMed
- Lancet. 2008 Oct 25;372(9648):1502-17 - PubMed
- Lancet. 2008 Jun 21;371(9630):2085-92 - PubMed
- CNS Drugs. 2011 Aug;25(8):673-98 - PubMed
- Eur J Neurol. 2006 Jun;13(6):604-10 - PubMed
- Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1716-20 - PubMed
- Am J Pathol. 2012 Jan;180(1):267-74 - PubMed
- Lancet Neurol. 2011 Jun;10(6):520-9 - PubMed
- Expert Rev Clin Pharmacol. 2012 May;5(3):245-56 - PubMed
- Neurology. 2005 Mar 22;64(6):987-91 - PubMed
- Expert Opin Investig Drugs. 2010 Dec;19(12):1603-12 - PubMed
- Am J Pathol. 2012 Aug;181(2):642-51 - PubMed
- Clin Neuropharmacol. 2011 Jan-Feb;34(1):28-35 - PubMed
- N Engl J Med. 2012 Sep 20;367(12):1098-107 - PubMed
- Expert Rev Neurother. 2005 Nov;5(6):721-7 - PubMed
- Acta Neuropathol. 2012 Sep;124(3):411-24 - PubMed
- Mult Scler. 2011 Nov;17(11):1341-50 - PubMed
- Acta Neurol Scand. 2011 Aug;124(2):75-84 - PubMed
- N Engl J Med. 2010 Feb 4;362(5):402-15 - PubMed
- J Neuroimmunol. 2012 Oct 15;251(1-2):14-24 - PubMed
- Mult Scler. 2010 Feb;16(2):197-207 - PubMed
- N Engl J Med. 2010 Feb 4;362(5):416-26 - PubMed
- Lancet. 1994 Jul 2;344(8914):9-13 - PubMed
- Neurology. 2012 Jun 5;78(23):1877-85 - PubMed
- N Engl J Med. 2006 Sep 14;355(11):1124-40 - PubMed
- Brain. 2011 Mar;134(Pt 3):678-92 - PubMed
- N Engl J Med. 2011 Oct 6;365(14):1293-303 - PubMed
- N Engl J Med. 2012 Mar 15;366(11):1000-9 - PubMed
- BMC Dev Biol. 2011 Jun 13;11:37 - PubMed
- N Engl J Med. 2012 Sep 20;367(12):1087-97 - PubMed
- N Engl J Med. 2010 Feb 4;362(5):387-401 - PubMed
- Clin Immunol. 2012 Jan;142(1):49-56 - PubMed
- Neurology. 2006 Mar 28;66(6):894-900 - PubMed
- Lancet Neurol. 2011 Apr;10(4):329-37 - PubMed
Publication Types