Drug treatment for spinal muscular atrophy type I

 

Abstract

Background

Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells of the spinal cord, which leads to progressive muscle weakness. Children with SMA type I will never be able to sit without support and usually die by the age of two years. There are no known efficacious drug treatments that influence the course of the disease. This is an update of a review first published in 2009.

Objectives

To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA type I, and to assess if such therapy can be given safely. Drug treatment for SMA types II and III is the topic of a separate updated Cochrane review.

Search methods

We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to 8 March 2011). We searched the Clinical Trials Registry of the U.S. National Institute of Health (www.ClinicalTrials.gov) (8 March 2011) to identify additional trials that had not yet been published.

Selection criteria

We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA type I. Participants had to fulfil the clinical criteria and have a deletion or mutation of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis.

The primary outcome measure was time from birth until death or full time ventilation. Secondary outcome measures were development of rolling, sitting or standing within one year after the onset of treatment, and adverse events attributable to treatment during the trial period.

Data collection and analysis

Two authors (RW and AV) independently reviewed and extracted data from all potentially relevant trials. For included studies, pooled relative risks and standardised mean differences were to be calculated to assess treatment efficacy.

Main results

One small randomised controlled study comparing riluzole treatment to placebo for 10 SMA type 1 children was identified and included in the original review. No further trials were identified for the update in 2011. Regarding the primary outcome measure, three of seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months, whereas all three children in the placebo group died; but the difference was not statistically significant. Regarding the secondary outcome measures, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand, and no adverse effects were observed. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and because of baseline differences. Follow-up of the 10 included children was complete.

Authors' conclusions

No drug treatment for SMA type I has been proven to have significant efficacy.

 

Plain language summary

Drug treatment for spinal muscular atrophy type I

Spinal muscular atrophy (SMA) is a severe neuromuscular disease with onset in childhood and adolescence that results in progressive muscle weakness. There are three main types of SMA. Drug treatment for SMA types II and III is discussed in a separate Cochrane review. The age of onset of SMA type I, also known as Werdnig-Hoffmann disease, is before six months. Children with SMA type I will never be able to sit without support and usually die by the age of two years. It is one of the most important causes of death due to a genetic disease in childhood. There was only one small randomised trial in the original review, which assessed the efficacy of riluzole for 10 children with SMA type I. In this trial all three children in the placebo group died, but three of the seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months. However, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and there were baseline differences that resulted in risk of bias. Evidence is insufficient to recommend riluzole for SMA type I. No further trials were identified for this 2011 update. No drug treatment has been shown to have significant efficacy for SMA type I.

 

摘要

背景

對於第一型脊髓肌肉萎縮的治療選擇

脊髓肌肉萎縮(SMA)是由於前角細胞的退化以導致持續性的肌肉無力。第一型SMA的小孩是無法不靠協助坐立，而且通常在兩歲的時候死亡。目前並無有效的藥物治療可影響病程。

目標

以評定藥物治療是否可延緩或停止第一型SMA的病程惡化，並評估其治療是否可安全的投予。對於第二和三型SMA的藥物治療將在另一篇Cochrane review討論到。

搜尋策略

我們查詢Cochrane Neuromuscular Disease Group Trials Register(2008年，9月30日)，Cochrane Library(2008年，第3冊)，MEDLINE(1966年1月至2008年6月)，EMBASE(1980年1月至2008年6月)，ISI(1988年1月至2008年6月)，以及ACP Journal Club(1991年1月至2008年6月)。

選擇標準

我們檢查關於所有對第一型SMA藥物治療的隨機或半隨機試驗。參與者必須符合臨床上的條件，並且有SMN1基因(5q11.2 – 13.2)的缺失或突變以在基因分析上確定診斷。主要結果是衡量從出生到死亡或完全依賴呼吸器的時間。次要結果是衡量在藥物治療後一年內發展至可自行滾動，坐或站，以及在試驗期間跟藥物有關的不良反應。

資料收集與分析

兩位作者(WB和AV)獨自回顧和擷取任何有關的資料。對於列入研究的相對風險和加權平均標準的差異來計算，以評估治療效果。

主要結論

我們取一個對於第一型SMA比較riluzole和安慰劑治療效果的小型隨機對照研究。對於主要結果的衡量，在七位孩子中有三位在給riluzole治療後可存活至30，48，和64個月，而另外給安慰劑的三位孩子則全部死亡，但統計上並沒有顯著意義的不同。針對次要重要的衡量，在給予riluzole或安慰劑後並沒有任何病人可發展至有能力去自行滾動，坐或站，而且也沒看到有不良反應。

作者結論

對於第一型SMA並沒有藥物治療可以被證實是有效的。

翻譯人

本摘要由新光醫院張安娜翻譯。

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

總結

對於第一型脊髓肌肉萎縮的治療選擇:脊髓肌肉萎縮(SMA)是一個起始於兒童和青春期而後發展成肌肉無力的嚴重神經肌肉病變。有三種的SMA。對於第二和三型SMA的藥物治療則在另一篇Cochrane review討論到。第一型SMA，又稱為WerdnigHoffmann disease，其起始為六歲前。第一型SMA的小孩是無法不靠協助坐立，而且通常在兩歲的時候死亡。這是其中一個最重要在兒童期基因型病變的死亡原因。只有一個小型隨機對照研究是對於第一型SMA病人給予riluzole後的效果。在這個研究中，給安慰劑的三位孩子全部死亡，但在七位孩子中有三位在給riluzole治療後可存活至30，48，和64個月。然而在給予riluzole或安慰劑後並沒有任何病人可發展至有能力去自行滾動，坐或站。在證據上並不足以建議對第一型SMA給予riluzole。對於第一型SMA並沒有藥物治療可以被證實是有效的。