Current and Emerging Therapies for the Treatment of Multiple Sclerosis: Focus on Cladribine

被引:4
作者
Schreiner, Teri L. [1 ]
Miravalle, Augusto [1 ]
机构
[1] Univ Colorado, Dept Neurol, Denver, CO 80202 USA
来源
JOURNAL OF CENTRAL NERVOUS SYSTEM DISEASE | 2012年 / 4卷
关键词
relapsing and remitting; progressive; multiple sclerosis; treatment; clinical trials; cladribine; methylprednisolone; Interferon beta 1b (Betaseron); Interferon beta 1a (Avonex); Interferon beta 1a (Rebif); glatiramer acetate (Copaxone); natalizumab (Tysabri); mitoxantrone (Novantrone); relapse rate; MRI; EDSS; disability progression; BG12; Laquinimod; Teriflunomide; fingolimod (Gilenya);
D O I
10.4137/JCNSD.S5128
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Multiple Sclerosis (MS) is a chronic inflammatory, immune-mediated, demyelinating disorder of the central nervous system with a heterogeneous clinical presentation and pathology in which activated lymphocytes play an important role in mediating tissue damage. Until recently, all first line therapies for MS were injectable. Several oral medications have been studied for preventative treatment of MS. Cladribine (2-chlorodeoxyadenosine) is a purine nucleoside analog that has been used for the treatment of several hematologic neoplasms, with a unique lymphcytotoxic mechanism of action. Cladribine has been investigated as treatment of MS for more than 15 years. A recent placebo-controlled, double-blind study of cladribine, CLARITY, showed decreased relapse rates, risk of disability progression and MRI measures of disease activity at 96 weeks. Cladribine's strengths included high efficacy and convenient, biannual oral dosing. However, concerns about safety prevented the FDA from approving cladribine in 2011. Thus, use of cladribine for treatment of relapsing and remitting multiple sclerosis will remain off-label.
引用
收藏
页码:1 / 14
页数:14
相关论文
共 50 条
[1]   Roles of immunoglobulins and B cells in multiple sclerosis: From pathogenesis to treatment [J].
Antel, Jack ;
Bar-Or, Amit .
JOURNAL OF NEUROIMMUNOLOGY, 2006, 180 (1-2) :3-8
[2]   CLADRIBINE (2-CHLORODEOXYADENOSINE) [J].
BEUTLER, E .
LANCET, 1992, 340 (8825) :952-956
[3]   The treatment of chronic progressive multiple sclerosis with cladribine [J].
Beutler, E ;
Sipe, JC ;
Romine, JS ;
Koziol, JA ;
McMillan, R ;
Zyroff, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (04) :1716-1720
[4]   Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3 [J].
Beyer, Marc ;
Classen, Sabine ;
Endl, Elmar ;
Kochanek, Matthias ;
Weihrauch, Martin R. ;
Debey-Pascher, Svenja ;
Knolle, Percy A. ;
Schultze, Joachim L. .
CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2011,
[5]   Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis [J].
Cohen, Jeffrey A. ;
Barkhof, Frederik ;
Comi, Giancarlo ;
Hartung, Hans-Peter ;
Khatri, Bhupendra O. ;
Montalban, Xavier ;
Pelletier, Jean ;
Capra, Ruggero ;
Gallo, Paolo ;
Izquierdo, Guillermo ;
Tiel-Wilck, Klaus ;
de Vera, Ana ;
Jin, James ;
Stites, Tracy ;
Wu, Stacy ;
Aradhye, Shreeram ;
Kappos, Ludwig .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (05) :402-415
[6]   Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial [J].
Comi, G. ;
Martinelli, V. ;
Rodegher, M. ;
Moiola, L. ;
Bajenaru, O. ;
Carra, A. ;
Elovaara, I. ;
Fazekas, F. ;
Hartung, H. P. ;
Hillert, J. ;
King, J. ;
Komoly, S. ;
Lubetzki, C. ;
Montalban, X. ;
Myhr, K. M. ;
Ravnborg, M. ;
Rieckmann, P. ;
Wynn, D. ;
Young, C. ;
Filippi, M. .
LANCET, 2009, 374 (9700) :1503-1511
[7]   Effect of early interferon treatment on conversion to definite multiple sclerosis:: a randomised study [J].
Comi, G ;
Filippi, M ;
Barkhof, F ;
Durelli, L ;
Edan, G ;
Fernández, O ;
Hartung, HP ;
Seeldrayers, P ;
Sorensen, PS ;
Rovaris, M ;
Martinelli, V ;
Hommes, OR .
LANCET, 2001, 357 (9268) :1576-1582
[8]  
Comi G, 2001, ANN NEUROL, V49, P290, DOI 10.1002/ana.64.abs
[9]  
Cook S., 2008, 60 ANN M AM AC NEUR, VP02. 180
[10]  
Cook SCG, 2011, 63 ANN M AM AC NEUR, VP04