Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis

  • Review
  • Intervention

Authors


Abstract

Background

Immunomodulatory drugs have been shown to be only modestly effective in clinically definite relapsing remitting multiple sclerosis (RRMS). It has been hypothesized that their efficacy could be higher if used at the first appearance of symptoms, that is in the clinically isolated syndromes (CIS) suggestive of demyelinating events, a pathology which carries a high risk to convert to clinically definite MS (CDMS).

Objectives

The objective of this review was to assess the effects of immunomodulatory drugs compared to placebo in adults in preventing conversion from CIS to CDMS which means the prevention of a second attack.

Search methods

We searched the Cochrane MS Group Trials Register (June 2007), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2007), MEDLINE (January 1966 to June 2007), EMBASE (January 1974 to June 2007) and reference lists of articles. We also contacted manufacturers and researchers in the field.

Selection criteria

The trials selected were double-blind, placebo-controlled, randomised trials of CIS patients treated with immunomodulatory drugs.

Data collection and analysis

Study selection have been independently done by two reviewers. Two further reviewers independently assessed trial quality and extracted and analysed data. Study authors were contacted for additional informations. Adverse effects information was collected from the trials.

Main results

Only three trials tested the efficacy of interferon (IFN) beta including a total of 1160 participants (639 treatment, 521 placebo); no trial tested the efficacy of glatiramer acetate (GA). The metanalyses showed that the proportion of patients converting to CDMS was significantly lower in IFN beta-treated than in placebo-treated patients both after one year (pooled OR 0.53; 95% CI, 0.40 to 0.71; p <0.0001) as well as after two years of follow-up (pooled OR 0.52; 95% CI, 0.38 to 0.70; p <0.0001). Early treatment with IFN beta was associated with the side effect profile reported by the randomised controlled trials with this drug. Since side effects were reported with some heterogeneity in the three studies the metanalysis was possible only for the frequency of serious adverse events, not significantly different in IFN beta-treated or placebo-treated patients.

Authors' conclusions

The efficacy of IFN beta treatment on preventing the conversion from CIS to CDMS was confirmed over two years of follow-up. Since patients had some clinical heterogeneity (length of follow-up, clinical findings of initial attack), it could be useful for the clinical practice to further analyse the efficacy of IFN beta treatment in different patient subgroups.

摘要

背景

Recombinant interferon beta 或 glatiramer 對於延緩第一次脫髓鞘事件發作演變成多發性硬化症的成效

免疫調節藥物已被證明對於臨床確診的復發緩解型多發性硬化症(relapsing remitting multiple sclerosis ,RRMS)只有輕微的療效。據推測如果用在第一次症狀出現時,其效力可能會更高,也就是用於代表脫髓鞘事件的臨床第一次症狀時(clinically isolated syndromes,CIS),這時,在病理變化上,其帶有高度的風險會轉換為臨床確診多發性硬化(clinically definite MS,CDMS)

目標

本回顧報告的目標是比較免疫調節藥物與安慰劑,在成人身上預防CIS演變成為CDMS的效果,其意味著防止再度發作。

搜尋策略

我們搜索的資料庫包過Cochrane MS Group Trials Register(2007年6月), Cochrane Central Register of Controlled Trials (CENTRAL)The Cochrane Library Issue 3, 2007, MEDLINE (1966年1月 to 2007年6月), EMBASE (1974年1月 to 2007年6月) 以及參考醫學文獻的列表。我們也連絡了藥廠及此一領域的研究專家。

選擇標準

我們選擇的臨床試驗為使用免疫抑制藥物治療CIS病人的雙盲、安慰劑對照、及隨機試驗。

資料收集與分析

兩位審查委員分別獨立選取研究報告。另外兩審查委員獨立評估試驗的品質和提取並分析數據。我們也連繫了研究的作者聯更多的信息。關於副作用的資訊則從試驗中收集。

主要結論

只有三項臨床試驗測試了干擾素(interferon,IFN)beta的療效,其中包括了一個共1160人參加的試驗(639人接受治療,521人接受安慰劑);沒有臨床試驗測試acetate (GA)的療效。統合分析的結果顯示,追蹤一年後,以IFN beta治療的病人轉換為CDMS的病人比例明顯低於安慰劑治療的患者(pooled OR 0.53; 95% CI, 0.40 to 0.71; p <0.0001)兩年後追蹤結果也類似(pooled OR 0.52; 95% CI, 0.38 to 0.70; p <0.0001)。早期使用IFN beta治療的副作用在這些隨機對照試驗中有被報告。由於在這三個臨床試驗中報告的副作用差異性相當大,本次統合分析的結果可能只適用於發生嚴重副作用的頻率,在這一部份,以IFN beta治療或以安慰劑治療的患者並無顯著差異。

作者結論

超過兩年的追蹤報告證實了IFN beta預防CIS演變成CDMS的療效。由於患者的臨床差異性(包括追蹤時間長短,初次發病的臨床症狀),臨床應用上可能還需要更多研究和分析,尤其是IFN beta使用在不同病患族群時。

翻譯人

本摘要由新光醫院鍾禎智翻譯。

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

總結

CIS的發生暗示了中樞神經系統的脫髓鞘變化,也帶有高度風險會轉化為CDMS。本次回顧分析發現,早期使用干擾素beta,對延緩第二次發作是有效的。然而仍需更多的研究,以評估干擾素和其他免疫調節劑的長期預防效果和劑量。目前沒有任何證據顯示,延緩第二次的臨床發作或MRI發作,就能夠延緩患者病情進展至失能及殘障狀態。

Plain language summary

Treatment of Multiple Sclerosis (MS) patients at a very early stage of the disease with recombinant interferon beta (IFN beta-1a and IFN beta-1b ) or glatiramer acetate (GA) could be useful in preventing irreversible damage in the central nervous system

Treatment of relapsing-remitting Multiple Sclerosis (RRMS) is currently based on immunomodulatory drugs such as recombinant interferon (IFN beta-1a and IFN beta-1b) or glatiramer acetate (GA) although these therapies have been shown to be only modestly effective. Recently it has been suggested that the nervous damage, supported by inflammation processes, is an early event in MS evolution which immunomodulatory drugs can only partially prevent. IFN and GA demonstrated only partial efficacy that could be ascribed to the fact that in the studies that lead to their approval they have been initiated in patients with a disease history of several years. The objective of this review was to assess IFN beta and GA efficacy in preventing the conversion to clinically defined multiple sclerosis in patients after the first demyelinating events. Among the pertinent literature, only three studies were found to test the efficacy of IFN beta including a total of 1160 participants (639 under treatment, 521 under placebo); while no published study testing the efficacy of GA was found. The review found that early interferon beta-1a treatment is effective in preventing the conversion of the first isolated demyelinating episodes into clinically definite MS both after one year and two years of follow-up. Side effects and adverse events occurrence was the same as reported by the many studies on IFN beta treatments in MS patients with different levels of the disease. More research is however needed to evaluate the long term preventing efficacy of these drugs and dosages.

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