Hartung H-P, Kieseier B C, Aktas O
Neurologische Klinik, Heinrich-Heine-Universität, Moorenstrasse 5, Düsseldorf, Germany.
Nervenarzt. 2010 Feb;81(2):194-202. doi: 10.1007/s00115-009-2878-y.
Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system in which autoreactive CD4(+) and CD8(+) T lymphocytes, B lymphocytes, macrophages, antibodies, and cytokines attack the myelin sheaths and damage the axons. The basic therapeutic agents and disease-modifying drugs that are currently available for MS require regular and frequent parenteral administration and therefore long-term compliance is unsatisfactory. Among all of the new oral MS agents presently under development, cladribine is the only substance that appears able to achieve long treatment-free intervals after only short-term administration. Cladribine is an immunomodulator with a long-lasting effect and a well-characterized safety profile based on over 15 years of experience with the parenteral route for MS and other indications. This contribution addresses the need for novel MS treatment approaches to improve compliance and describes the mechanism of action of cladribine, the available data on effectivity and safety, and the clinical development of the oral formulation of cladribine. The results from the recently published 96-week, double-blind, randomized, placebo-controlled, multicenter study CLARITY (CLAdRIbine Tablets Treating MS OrallY) are very promising. They clearly show that oral cladribine reduces relapse rate, disability progression and disease activity and burden as evidenced by MRI.
多发性硬化症(MS)是一种慢性、免疫介导的中枢神经系统疾病,其中自身反应性CD4(+)和CD8(+) T淋巴细胞、B淋巴细胞、巨噬细胞、抗体和细胞因子攻击髓鞘并损害轴突。目前可用于MS的基本治疗药物和疾病修饰药物需要定期且频繁地进行肠胃外给药,因此长期依从性并不理想。在目前正在研发的所有新型口服MS药物中,克拉屈滨是唯一一种似乎仅在短期给药后就能实现长时间无治疗间隔的药物。基于超过15年将肠胃外给药用于MS和其他适应症的经验,克拉屈滨是一种具有持久作用且安全性特征明确的免疫调节剂。本文论述了对新型MS治疗方法以提高依从性的需求,并描述了克拉屈滨的作用机制、有效性和安全性的现有数据,以及克拉屈滨口服制剂的临床开发情况。最近发表的为期96周的双盲、随机、安慰剂对照、多中心研究CLARITY(口服克拉屈滨片治疗MS)的结果非常有前景。这些结果清楚地表明,口服克拉屈滨可降低复发率、残疾进展以及疾病活动和负担,MRI结果证明了这一点。