Lublin Fred
Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai Medical Center, New York, NY 10029-6574, USA.
J Neurol. 2005 Sep;252 Suppl 3:iii3-iii9. doi: 10.1007/s00415-005-2010-6.
Although the earliest recorded description of multiple sclerosis (MS) dates back to the 14(th) century, it was not until the latter years of the 20(th) that treatments for this disabling condition were found. However, the "road to success" has not been without hurdles. Trials with both interferon alpha and gamma proved unsuccessful, as did treatment with oral myelin, cladribine, sulfasalazine and inhibitors of tumour necrosis factor. In 1993, interferon beta-1b (IFNbeta-1b) became the first therapy proven to be effective in altering the natural history of relapsing-remitting MS (RRMS). This was followed by successful trials with IFNbeta-1a and glatiramer acetate. In 1998, a European trial showed IFNbeta-1b to be also beneficial in the treatment of secondary progressive MS (SPMS). A similar trial in North America failed to reach its primary endpoint but was effective across secondary endpoints, highlighting how different methodology and patient populations can lead to inconsistent results and, thus, making comparisons across trials difficult. The trend for early intervention in MS with IFNbeta was recently supported by the CHAMPS (Controlled High-risk Avonex MultiPle Sclerosis) and ETOMS (Early Treatment of Multiple Sclerosis) studies using once-weekly IFNbeta-1a. Both trials demonstrated delayed conversion to clinically definite MS in patients with a clinically isolated syndrome and magnetic resonance imaging (MRI) findings suggestive of MS. Two directly comparative trials of high- (250 microg IFNbeta-1b or 44 microg IFNbeta-1a) and low-dose (30 microg IFNbeta-1a) IFNbeta (INCOMIN [INdependent COMparison of INterferons] and EVIDENCE [EVidence of Interferon Dose-response: European North American Comparative Efficacy]) support the superior efficacy of the higher dose and/or more frequent administration for treating RRMS. Since MS entered the treatment era in 1993, therapies for RRMS, SPMS and, more recently, progressive- relapsing MS have been developed. There is now a much better understanding of the pathogenesis of the disease, but new and improved therapeutic approaches are still needed.
虽然对多发性硬化症（MS）最早的记录描述可追溯到14世纪，但直到20世纪后期才找到针对这种致残病症的治疗方法。然而，“通往成功之路”并非一帆风顺。α干扰素和γ干扰素的试验均告失败，口服髓磷脂、克拉屈滨、柳氮磺胺吡啶以及肿瘤坏死因子抑制剂的治疗效果也不佳。1993年，β-1b干扰素（IFNβ-1b）成为首个被证实能有效改变复发缓解型多发性硬化症（RRMS）自然病程的疗法。随后，IFNβ-1a和醋酸格拉替雷的试验也取得了成功。1998年，一项欧洲试验表明IFNβ-1b对继发进展型多发性硬化症（SPMS）的治疗也有益处。北美进行的一项类似试验未达到其主要终点，但在次要终点方面有效，这凸显了不同的方法和患者群体如何导致结果不一致，从而使得不同试验之间的比较变得困难。最近，使用每周一次的IFNβ-1a的CHAMPS（对照高风险阿沃尼单抗多发性硬化症）和ETOMS（多发性硬化症早期治疗）研究支持了MS早期使用IFNβ进行干预的趋势。两项试验均表明，对于患有临床孤立综合征且磁共振成像（MRI）结果提示MS的患者，向临床确诊MS的转化有所延迟。两项关于高剂量（250微克IFNβ-1b或44微克IFNβ-1a）和低剂量（30微克IFNβ-1a）IFNβ的直接对比试验（INCOMIN [干扰素独立对比试验]和EVIDENCE [干扰素剂量反应证据：欧洲北美对比疗效试验]）支持了高剂量和/或更频繁给药在治疗RRMS方面的卓越疗效。自1993年MS进入治疗时代以来，针对RRMS、SPMS以及最近的进展复发型MS的疗法不断涌现。目前对该疾病的发病机制有了更好的理解，但仍需要新的和改进的治疗方法。
