Recent advances in treating multiple sclerosis: efficacy, risks and place in therapy

被引:20
作者
Jeffery, Douglas R. [1 ]
机构
[1] Cornerstone Hlth Care, Adv Neurol, MS Ctr, 152 Kinderton Way,Suite 101, Advance, NC 27006 USA
关键词
BG-12; fingolimod; fumarate; JC virus; multiple sclerosis; natalizumab; progressive multifocal leukoencephalopathy; teriflunomide;
D O I
10.1177/2040622312466279
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The development of new pharmacologic agents for the treatment of multiple sclerosis (MS) and advances in testing for exposure to the JC virus have led to changes in the treatment of MS. In addition several new agents are in late stage development for MS and their entry onto the market will provide additional treatment options. In 2012 and in early 2013, it is likely that both terifunomide and BG-12 will be approved by the United States Food and Drug Administration (FDA) for the treatment of relapsing forms of MS. The therapeutic environment has already changed and is likely to change rapidly over the next several years. Fingolimod was the first oral agent approved for the treatment of MS and this agent is now widely used in patients intolerant of injections and the side effects associated with the older platform therapies. In many settings it is also used a first-line agent. Owing to the risk of progressive multifocal leukoencephalopathy, natalizumab had previously been reserved for patients with active disease who were intolerant of first-line agents or patients who were worsening despite standard therapy. With the availability of JC virus antibody testing, natalizumab is now being used as a first-line agent in patients negative for JC virus antibodies. Teriflunomide and BG-12 will become available in the next year. Both agents have suitable efficacy and a favorable safety and tolerability profile. There are advantages and disadvantages associated with all of the oral agents. In this article we summarize the clinical trial results regarding the efficacy and safety of the oral agents and discuss the changes that are already taking place in the therapeutic landscape for MS.
引用
收藏
页码:45 / 51
页数:7
相关论文
共 24 条
[1]  
Bozic C., Richman S., Plavina T., Natarajan A., Scanlon J., Subramanyam M., Et al., Anti-John Cunningham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY-1, Ann Neurol, 70, pp. 742-750, (2011)
[2]  
Coelho R., Payne S., Bittman R., Spiegel S., Sato-Bigbee C., The immunomodulator FTY 720 has a direct cytoprotective effect in oligodendrocyte progenitors, J Pharmacol Exp Ther, 323, pp. 626-635, (2007)
[3]  
Cohen J., Barkhof F., Comi G., Hartung H., Khatri B., Montalban X., Et al., Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis, N Eng J Med, 362, pp. 402-415, (2010)
[4]  
Chun J., Hartung H., Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis, Clin Neuropharacol, 33, pp. 91-101, (2010)
[5]  
de Jong R., Bezemer A., Zomerdijk T., van de Pouw-Kraan T., Ottenhoff T., Nibbering P., Selective stimulation of T helper 2 cytokine responses by the anti-psoriasis agent monomethylfumarate, Eur J Neurol, 26, pp. 2067-2074, (1996)
[6]  
Foster C., Howard L., Schweitzer A., Persohn E., Hiestand P., Balatoni B., Et al., Brain penetration of the oral immunomodulatory drug FTY 720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis, J Pharmacol Exp Ther, 323, pp. 626-635, (2007)
[7]  
Fox R., Herrmann M., Frangou C., Wahl G., Morris R., Strand V., Et al., Mechanism of action for leflunomide in rheumatoid arthritis, Clin Immunol, 93, pp. 198-208, (1999)
[8]  
Fox R., Rudick R., Risk stratificationand patient counseling for natalizumab in multiple sclerosis, Neurology, 78, pp. 436-437, (2012)
[9]  
Gardell S., Choi J., Herr D., Anliker B., Lu M., Kennedy G., Et al., Evidence for neural S1P receptor signaling in EAE and FTY 720 efficacy, Mult Scler, 13, (2007)
[10]  
Hutchinson M., Kappos L., Calabresi P., Confavreux C., Giovannoni G., Galetta S., Et al., The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL, J Neurol, 256, pp. 405-415, (2009)