复发缓解型多发性硬化症每月静脉注射免疫球蛋白治疗的随机安慰剂对照试验。奥地利免疫球蛋白治疗多发性硬化症研究组。

Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group.

作者信息

Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B

机构信息

Department of Neurology, Karl-Franzens University, Graz, Austria.

出版信息

Lancet. 1997 Mar 1;349(9052):589-93. doi: 10.1016/s0140-6736(96)09377-4.

DOI:10.1016/s0140-6736(96)09377-4

PMID:9057729

Abstract

BACKGROUND

Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study.

METHODS

Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score).

FINDINGS

Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication.

INTERPRETATION

Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.

摘要

背景

多发性硬化症是一种自身免疫性疾病，其特征是中枢神经系统内反复出现脱髓鞘病变。非对照研究和实验证据表明，通过免疫调节机制以及诱导或促进髓鞘再生，反复静脉注射免疫球蛋白（IVIg）具有有益效果。我们旨在通过一项随机双盲多中心研究来调查IVIg的疗效。

方法

复发缓解型多发性硬化症患者被随机分配，每月接受一次IVIg（0.15 - 0.2 g/kg体重）或安慰剂治疗。治疗持续时间为2年。主要结局指标为治疗对临床残疾的影响（通过Kurtzke扩展残疾状态量表（EDSS）评分的绝对变化来衡量）以及临床残疾改善、稳定或恶化的患者比例（EDSS评分≥1.0级）。

研究结果

在筛选的243例患者中，150例符合我们的纳入标准，并被随机分配至IVIg组或安慰剂组。治疗开始前，安慰剂组有2例患者退出，因此IVIg组有75例患者，安慰剂组有73例患者。意向性分析表明，IVIg治疗对临床残疾病程有有益影响。接受IVIg治疗的患者EDSS评分下降，而安慰剂组上升（-0.23 [95%可信区间 -0.43至 -0.03] 对比0.12 [-0.13至0.37]，p = 0.008）。在IVIg组，临床残疾改善、稳定或恶化的患者数量分别为23例（31%）、40例（53%）和12例（16%），而安慰剂组分别为10例（14%）、46例（63%）和17例（23%）。接受IVIg治疗的3例（4%）患者和安慰剂组的4例（5%）患者报告了副作用，但与研究用药无直接关联。