Glucocorticoid corticosteroids for Duchenne muscular dystrophy

  • Review
  • Intervention

Authors


Abstract

Background

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. This incurable disease is characterised by muscle wasting and loss of walking ability leading to complete wheelchair dependence by 13 years of age. Prolongation of walking is one of the major aims of treatment.

Objectives

The aim of this review was to assess whether glucocorticoid corticosteroids stabilize or improve muscle strength and walking in boys with DMD.

Search methods

This is an update of the Cochrane systematic review first published in 2004 (Manzur 2004). We searched the Cochrane Neuromuscular Disease Group Trials Register (August 2006) using the term 'Duchenne muscular dystrophy'. We also searched MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to August 2006), CINAHL and LILACS (January 1982 to August 2006). We wrote to authors of published studies and other experts in this disease to help identify other trials, checked the references in the identified trials and hand searched the abstracts of relevant journals.

Selection criteria

Types of studies: randomised or quasi-randomised trials.
Types of participants: all patients with a definite diagnosis of Duchenne muscular dystrophy.
Types of interventions: glucocorticoids such as prednisone, prednisolone, deflazacort or others, with a minimum treatment period of three months.
Primary outcome measure: prolongation of walking (independent walking without long leg calipers).
Secondary outcome measures: strength outcome measures, manual muscle strength testing using Medical Research Council strength scores, functional outcome measures and adverse events.

Data collection and analysis

We identified six randomised controlled trials that met the inclusion criteria for our review, and one of these (Beenakker 2005) is a new addition to this update, as it was published subsequent to our first review (Manzur 2004). Two review authors independently selected the trials for the review and assessed methodological quality. Data extraction and inputting were double-checked.

Main results

Primary outcome measure: data from one small study used prolongation of walking as an outcome measure and did not show significant benefit.

Secondary outcome measures: The meta-analysis of the results from four randomised controlled trials with altogether 249 participants showed that glucocorticoid corticosteroids improved muscle strength and function over six months. Improvements were seen in time taken to rise from the floor (Gowers' time), nine metres walking time, four-stair climbing time, ability to lift weights, leg function grade and forced vital capacity. One randomised controlled trial with altogether 28 participants showed that glucocorticoid corticosteroids stabilize muscle strength and function for up to two years. The most effective prednisolone regime appears to be 0.75 mg/kg/day, given in a daily dose regime. Not enough data were available to compare efficacy of prednisone with deflazacort.

Adverse effects: Excessive weight gain, behavioural abnormalities, cushingoid appearance and excessive hair growth were all more common with glucocorticoid corticosteroids than placebo. Long-term adverse effects of glucocorticoid therapy could not be evaluated because of the short-term duration of the randomised studies.

Non-randomised studies: A number of non-randomised studies with important efficacy and adverse effects data are tabulated and discussed.

Authors' conclusions

There is evidence from randomised controlled studies that glucocorticoid corticosteroid therapy in Duchenne muscular dystrophy improves muscle strength and function in the short-term (six months to two years). The most effective prednisolone regime appears to be 0.75 mg/kg/day, given daily. In the short term, adverse effects were significantly more common but not clinically severe. Long-term benefits and hazards of glucocorticoid treatment cannot be evaluated from the currently published randomised studies. Non-randomised studies support the conclusions of functional benefits but also identify clinically significant adverse effects of long-term treatment. These benefits and adverse effects have implications for future research studies and clinical practice.

摘要

背景

醣皮質激素類固醇使用於杜馨氏失養症

杜馨氏肌失養症(DMD)是小孩中最常見的肌肉失養症.這無法治癒的疾病特徵是肌肉耗損和喪失行走能力,導致13歲前完全要倚靠輪椅.延長行走的能力是主要治療的目標.

目標

這項回顧的目的是評估醣皮質激素類固醇是否能穩定或改善有DMD男孩的肌肉力量和行走能力.

搜尋策略

這是第一次被發表在the Cochrane systematic review 2004年的更新版 (Manzur 2004).我們使用了‘杜馨氏肌失養症‘的名詞搜尋了the Cochrane Neuromuscular Disease Group Trials Register (August 2006). 我們也搜尋了MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to August 2006), CINAHL and LILACS (January 1982 to August 2006).為了幫助辨認出其他試驗,我們寫信給刊出研究的作者和其他在這個疾病的專家,檢查了在這些試驗的參考資料和手動收尋了相關期刊的摘要.

選擇標準

研究的類型:隨機或半隨機的試驗.受試者的類型:所有明確診斷是DMD的病人.治療的類型:醣皮質激素像prednisone, prednisolone, deflazacort或其他等,至少治療3個月.初級的結果分析的是:延長行走的能力(不靠長腿金屬夾獨立的行走).次級的結果分析的是:力量結果分析,使用Medical Research Council strength scores作的徒手肌肉力量測試,功能性結果分析和副作用.

資料收集與分析

我們找到6個隨機對照組試驗符合我們回顧分析的收錄標準,而其中一個(Beenakker 2005)是新加入的更新版,因為它在我們第一次回顧(Manzur 2004)後才被刊登出來。兩個負責回顧的作者獨立的選擇試驗和評估方法學的品質,並重複確認被擷取和輸入的資料。

主要結論

初級的結果分析是:從一個把延長行走能力當作結果分析的小型研究中,顯示沒有顯著的益處。次級的研究結果分析:從4個總共249個受試者的隨機對照組試驗綜合分析,顯示醣皮質激素類固醇可以改善肌肉的力量和功能超過6個月。客觀改善指標包括從地板上爬起的時間Gowers’ time)、9公尺的走路時間、爬4層樓梯的時間、提重物的能力、小腿功能分級和肺活量。一個有28個受試者的的隨機試驗顯示醣皮質激素類固醇穩定肌肉的力量和功能達2年之久。最有效的類固醇劑量是0.75 mg/kg/天,以每天的方式給予。沒有足夠的資料可以比較prednisone 和 deflazacort的效果。副作用:過度的體重增加、行為異常、庫欣氏外表和過度的毛髮生長,在醣皮質激素類固醇組都比安慰組更常見。因為這些隨機試驗都是短期的,長期的醣皮質激素類固醇副作用無法被評估。非隨機試驗:一些有重要效果和副作用的非隨機試驗的資料被製成表格和討論。

作者結論

在隨機對照組研究中證實醣皮質激素類固醇治療可以改善DMD短期的肌肉力量和功能(6個月到2年),最有效的類固醇劑量是0.75 mg/kg/天,每天給予。短期來說,副作用是顯著的且常見的,但臨床上不是很嚴重。長期醣皮質激素治療的好處和壞處無法從目前發表的隨機研究來評估。非隨機研究支持醣皮質激素類固醇治療有功能上的好處,但也發現到有長期治療的顯著臨床副作用,這些好處和副作用為將來的研究和臨床應用提供了啟發意義。

翻譯人

本摘要由新光醫院李建欣翻譯。

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

總結

醣皮質激素類固醇治療可以改善DMD的肌肉力量和功能6個月到2年. DMD是小孩中無法治癒的疾病.肌肉耗損和喪失行走能力導致倚靠輪椅和最後的死亡.醣皮質激素增加肌力的精確方式是未知的.隨機對照組試驗顯示醣皮質激素類固醇可以改善肌肉力量和功能6個月到2年.短期副作用是顯著的但不嚴重而且可以被處理.從非隨機對照組的研究資料顯示在有治療的病人有超過5年的功能上的改善,但整體的長期好處仍然不清楚,而且必須和這些藥物的長期副作用作權衡.用來釐清這個不確定性的隨機對照組研究是需要的,但是需要小心道德上的考量.

Plain language summary

Glucocorticoid corticosteroid therapy in Duchenne muscular dystrophy (DMD) improves muscle strength and function for six months to two years.

Duchenne muscular dystrophy is an incurable disease of childhood. Muscle wasting and loss of walking lead to wheelchair dependence and eventually death. The precise way in which glucocorticoids increase strength is unknown. Randomised controlled trials have shown that glucocorticoid corticosteroids improved muscle strength and function for six months to two years. Short-term side effects were significant but not severe and could be managed. Data from non-randomized studies suggests functional benefit over a five year period in many treated patients, but the overall long-term benefit remains unclear, and has to be weighed against the long-term side effects of these drugs. Randomised controlled trials to clarify this uncertainty are desirable, but would require careful ethical consideration.

Ancillary