Dudesek Ales, Zettl Uwe K
Department of Neurology, University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany.
J Neurol. 2006 Sep;253 Suppl 5:V50-8. doi: 10.1007/s00415-006-5007-x.
Treatment of neurological disorders with intravenous immunoglobulin (IVIG) is an increasing feature of practice for an expanding range of indications. This article reviews the current literature regarding the role of IVIG treatment in multiple sclerosis (MS) and summarizes recommendations for the use of IVIG in different courses and clinical subsets of the disease. Principally based on the results of four randomized, double-blind, placebo-controlled trials (RCTs) and a corresponding meta-analysis, the amount of evidence for the efficacy of IVIG treatment is currently most convincing for the relapsing-remitting course of MS (RRMS); nevertheless, it lags clearly behind that for beta interferon due to smaller study sizes, partial deficits in study design and not established optimal dosage. This prompted the basis for a consensus statement in some countries to recommend IVIG as second-line treatment in RRMS, when other licensed therapies (i. e., beta interferon, glatiramer acetate) are individually not tolerated due to side effects or concomitant disease. Recent evidence indicates that IVIG is also effective in clinically isolated syndrome (CIS) and should be considered as a therapeutic option, particularly when licensed immunotherapy can not be offered. During an acute relapse additional IVIG administration to established steroid treatment showed no benefit. Despite promising experimental data on promotion of remyelination, fixed chronic deficits were not reversed or improved by long-term IVIG treatment either. Currently there is no indication for IVIG treatment in the chronic progressive disease stages, since a large and well-designed RCT failed to show any beneficial effect in patients with secondary progressive MS (SPMS) and data derived from primary progressive MS (PPMS) are still pending. However, preliminary results of a so far unpublished RCT including patients with PPMS and SPMS suggest a strong trend towards a beneficial effect in PPMS. So far, IVIG is the only therapy investigated for reducing postpartum relapses, whereas immunomodulatory drugs are contraindicated during pregnancy and lactation period. Data evaluating the peripartal use of IVIG along with the positive results of the trials in RRMS justify postpartal IVIG treatment particularly for mothers, who choose to breastfeed, under consideration of the recommendations specified for the relapsing-remitting disease course. As recently shown IVIG administration right from the early weeks of pregnancy appears to be a promising strategy, but cannot be recommended from the viewpoint of evidence-based medicine.
静脉注射免疫球蛋白（IVIG）治疗神经系统疾病在越来越多的适应症中成为临床实践的一个特点。本文综述了当前关于IVIG治疗在多发性硬化症（MS）中作用的文献，并总结了在该疾病不同病程和临床亚组中使用IVIG的建议。主要基于四项随机、双盲、安慰剂对照试验（RCT）的结果以及相应的荟萃分析，目前IVIG治疗疗效的证据量在复发缓解型MS（RRMS）中最有说服力；然而，由于研究规模较小、研究设计存在部分缺陷且未确定最佳剂量，其证据明显落后于β干扰素。这促使一些国家达成共识声明，建议在RRMS中，当其他获批疗法（即β干扰素、醋酸格拉替雷）因副作用或合并症而个体不耐受时，将IVIG作为二线治疗。最近的证据表明，IVIG在临床孤立综合征（CIS）中也有效，应被视为一种治疗选择，特别是在无法提供获批免疫疗法时。在急性复发期间，在已有的类固醇治疗基础上加用IVIG并无益处。尽管有关于促进髓鞘再生的有前景的实验数据，但长期IVIG治疗也未能逆转或改善固定的慢性缺陷。目前，在慢性进展性疾病阶段尚无IVIG治疗的指征，因为一项大型且设计良好的RCT未能在继发进展型MS（SPMS）患者中显示出任何有益效果，而原发进展型MS（PPMS）的数据仍有待确定。然而，一项尚未发表的包括PPMS和SPMS患者的RCT的初步结果表明，PPMS有明显的获益趋势。到目前为止，IVIG是唯一被研究用于减少产后复发的疗法，而免疫调节药物在妊娠和哺乳期是禁忌的。评估围产期使用IVIG的数据以及RRMS试验的阳性结果证明了产后IVIG治疗的合理性，特别是对于选择母乳喂养的母亲，需考虑复发缓解型病程的特定建议。最近的研究表明，从妊娠早期就开始使用IVIG似乎是一种有前景的策略，但从循证医学的角度来看，目前还不能推荐。
