Intravenous immunoglobulins for multiple sclerosis

 

Abstract

Background

Animal experiments suggest that intravenous immunoglobulins can reverse some of the disease process of central nervous system demyelination. Subsequently, clinical trials of intravenous immunoglobulins have been conducted in people with multiple sclerosis (MS).

Objectives

To identify and summarise the evidence that intravenous immunoglobulins are safe and beneficial for people with MS.

Search methods

We searched the Cochrane Multiple Sclerosis Group Trials Register (Jan 2009), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2008, issue 4", MEDLINE (PubMed) (1996 - Jan 2009), and EMBASE (1974 - Jan 2009). Reference lists of retrieved studies, reviews and conference abstracts were considered and relevant pharmaceutical companies contacted.

Selection criteria

Randomised controlled trials of intravenous immunoglobulins for the prevention of relapses and disease progression in MS.

Data collection and analysis

All authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.

Main results

Ten randomised double-blinded trials were identified and suitable for consideration by this review. Four trials were excluded as they did not use outcome measures specified (2 trials, 122 participants), or were of insufficient methodological quality (2 trials, 34 participants). The remaining six trials met our inclusion criteria. These included four with relapsing remitting cases (367 participants) and two with secondary progressive cases (515 participants), one of which had also primary progressive cases (34 participants).

In the relapsing remitting group there was a reduction in relapse rate (WMD -0.72 95% CI -0.78 to -0.66), increased time to first relapse and higher proportion of cases remaining relapse free (OR 0.63 95%CIs 0.42-0.94) during treatment with intravenous immunoglobulins. There is no robust data on disease progression in this group. In the secondary progressive group treatment had no impact on sustained EDSS progression (OR 0.96 95%CIs 0.68-1.37). Fewer primary progressive patients treated with immunoglobulin progressed that those in the placebo group (p=0.016). There is conflicting evidence of reduction in number of new lesions on T2 weighted MRI and gadolinium enhancing lesions on T1 weighted MRI and total MRI lesion burden in relapsing remitting MS but no evidence in secondary progressive disease.

Authors' conclusions

There is evidence to support use of intravenous immunoglobulins as a preventative treatment for relapses in relapsing remitting MS. There was no evidence of delay in progression of disease in secondary progressive MS, but this needs to be evaluated in relapsing remitting disease. Immunoglobulins were well tolerated with a less than 5% risk of drug related adverse events in participants in included trials.

 

Plain language summary

The use of immunoglobulins (antibodies) for treating people with multiple sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated disease of the nervous system that affects young and middle-aged adults and can lead to permanent disability. Immunoglobulins have several effects on the immune system, and help fight infections. The review of trials found there is some evidence that immunoglobulins can reduce the rate of relapses in people who have relapsing remitting MS. There is no evidence that immunoglobulins can reduce the progression of MS.

 

摘要

背景

用靜脈免疫球蛋白治療多發性硬化症

從動物實驗結果中，顯示靜脈注射免疫球蛋白可以逆轉一些中樞神經脫髓鞘病變的病程。因此，以靜脈注射免疫球蛋白治療多發性硬化症病人的臨床試驗也就陸續問市。

目標

為了找出並整理出靜脈注射免疫球白對MS病人安全且有效的證據。

搜尋策略

我們搜尋了the Cochrane Multiple Sclerosis Group trials Register(January 2003) The Cochrane Central Register of Controlled Trials (The Cochrane Library issue 4, 2002), MEDLINE (January 1966 to April 2001), EMBASE (January 1988 to April 2001)等資料庫以及其中文章的參考文獻列表。我們也聯絡了相關的製藥公司和所選試驗的作者。

選擇標準

研究以靜脈注射免疫球蛋白預防MS 再發及避免疾病進展的隨機分配試驗

資料收集與分析

我們從文獻搜索中找到913篇文章標題和摘要，最後從中找到10個臨床試驗。所有評論者都達成共識的數據則鍵入Rev Man 4.1資料庫中，並整理出結果。我們為了獲得論文以外的額外資訊，主動聯絡試驗的作者，但是沒有得到回應。

主要結論

在全部913個可能相關的研究中，找到10個臨床試驗符合本文的研究條件，總共有918個病人，其中4個臨床試驗正在進行中或正在等待論文的發表。剩下的6個試驗則被本篇評論考慮收金，總共有344個病人。最後只有兩個試驗達到我們的收案標準。其他的4 個試驗中，有2個試驗，包括122個病人，因沒有使用我們研究評論所要求的結果指標而被排除，另外2個試驗，包括34個病人，則因研究方法的品質不良而被排除。在最後被本文收錄的2 個試驗共168個病人中，顯示使用靜脈注射免疫球蛋白期間，再發率有減少，到第一次復發的時間也有延長，但是沒有可靠的疾病進展結果報告，也沒有核磁共振(MRI)的數據來支持臨床的表現。迄今，仍在進行中或是已完成但尚未發表的試驗中仍有多達574個病人。

作者結論

有證據支持使用靜脈注射免疫球蛋白可以預防復發/緩解型MS的復發，但是接下來應該有更進一步的試驗使用MRI 和疾病的進展作為觀察研究的終點。等現今正在進行或是最近剛作完的試驗公布數據之後，將可能得到更確切的結論。目前已經完成的兩個嚴格執行的試驗中共含122個病人，未能顯示正面的臨床效果，但是因為它們使用了本評論計畫中未包含的結果指標，所以被排除在本評論之外。在所有登錄的試驗中，參與者對免疫球蛋白耐受度良好。免疫球蛋白引起不良反應的機率低於5%。

翻譯人

本摘要由新光醫院葉旭霖翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

免疫球蛋白可以幫助減少多發性硬化症患者的復發，但是要斷定它們可不可以有效地治療這個疾病還言之過早。多發性硬化症(MS)是一個影響年輕人和中年人的慢性神經系統疾病，MS 破壞神經傳導電子訊號的能力，而且能導致永久的失能。MS 可能和免疫系統有關。免疫球蛋白(抗體)對於免疫系統有數種作用，可以幫助對抗感染。這篇評論發現有證據顯示免疫球蛋白可以減少進入緩解期MS病人復發的機率。沒有強烈的證據顯示免疫球蛋白可以減慢MS 的進展或是逆轉已經存在的損害。其他試驗正在進行中。