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Intervention Review

Mitoxantrone for multiple sclerosis

  1. Filippo Martinelli Boneschi1,*,
  2. Marco Rovaris2,
  3. Ruggero Capra3,
  4. Giancarlo Comi4

Editorial Group: Cochrane Multiple Sclerosis Group

Published Online: 19 OCT 2005

Assessed as up-to-date: 23 AUG 2005

DOI: 10.1002/14651858.CD002127.pub2


How to Cite

Martinelli Boneschi F, Rovaris M, Capra R, Comi G. Mitoxantrone for multiple sclerosis. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD002127. DOI: 10.1002/14651858.CD002127.pub2.

Author Information

  1. 1

    INSPE - San Raffaele Scientific Institute, Department of Neurology, Milano, Italy

  2. 2

    San Raffaele Institute, Neuroimaging Research Unit, Milano, Italy

  3. 3

    Spedali Civili, Brescia, Italy

  4. 4

    San Raffaele Hospital, Department of Neurology, Milano, Italy

*Filippo Martinelli Boneschi, Department of Neurology, INSPE - San Raffaele Scientific Institute, Via Olgettina, 48, Milano, 20131, Italy. filippo.martinelli@hsr.it.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 OCT 2005

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This is not the most recent version of the article. View current version (31 MAY 2013)

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients.

Objectives

The objective was to assess the efficacy and safety of MX in relapsing-remitting MS (RRMS), progressive relapsing MS (PRMS) and secondary progressive MS (SPMS).

Search methods

We searched the Cochrane MS Group Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med) (January 1966 to April 2005), EMBASE (January 1974 to April 2005), and reference lists of articles. We also undertook hand searching and contacting trialists and pharmaceutical companies.

Selection criteria

The trials were selected if double-blinded, placebo-controlled, randomised, irrespective of eventual additive therapy (such as steroids).

Data collection and analysis

Three reviewers independently selected articles for inclusion, assessed trials' quality and extracted data.

Main results

Four trials involving 270 participants were included. MX reduced the progression of disability at 2 years follow-up (proportion of participants with 6-months confirmed progression of disability: Odds Ratios (OR) 0.3, p = 0.05). Similar figures were found regarding the reduction in annualised relapse rate, the proportion of patients free from relapses at 1 and 2 years, and the number of patients with active MRI lesions at 6 months/ 1 year only. Side effects reported in the trials were more frequent in treated patients than in controls. Caution must be exercised in drawing conclusions from such data because of the heterogeneous quality and characteristics of the included trials. Moreover, from the included trials, it was not possible to estimate the long-term efficacy and safety of MX.

Authors' conclusions

MX is moderately effective in reducing the disease progression and the frequency of relapses in patients affected by RR, PR and SP MS in the short-term follow-up (2 years), even if the results are based on trials heterogeneous in terms of drug dosage and inclusion criteria. No major neoplastic or symptomatic cardiotoxicity related to MX have been reported from the trials. However, longer follow-up studies are highly warranted to better explore the efficacy and safety of the drug, mainly as regards the long-term risk of therapy-related leukemias and cardiotoxicity which is increasingly reported in the literature.
As a conclusion, MX has a partial efficacy, but, due to its unclear long-term safety profile, it should be used to treat patients with worsening RR and SP MS with evidence of worsening disability.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

The use of the immunosuppressive drug Mitoxantrone (MX) in people with multiple sclerosis (MS)

MS is an immune-mediated chronic disorder of the central nervous system (CNS) characterized by multiple areas of inflammation and demyelination. MS is among the commonest causes of neurological disability in young people. Steroids, interferon and other drugs have been used to treat specific symptoms. This review determined that MX, widely used for treatment of breast cancer and leukaemia, was moderately effective in the short-term treatment of MS. The most frequent side-effects are transitory amenorrhoea, nausea and vomiting, alopecia, urinary tract infections and transitory leucopenia. However, caution must be exercised when interpreting these results, because of the heterogeneous quality and characteristics of the included trials, which are different in terms of treatment schedule and type of enrolled patients. Moreover, there are little information on the long term effects of MX, especially as regards the risk of cardiotoxicity and therapy-related acute leukemias, which is increasingly reported in the literature.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以Mitoxantrone治療多發性硬化症

Mitoxantrone(MX)顯示可以減輕多發性硬化症的臨床疾病活性。

目標

目標是評估MX在復發緩解型MS(RRMS), 漸進復發型MS(PRMS)和次發漸進型MS(SPMS)的療效和安全性。

搜尋策略

我們在Cochrane MS Group Trials Register(searched April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med)(January 1966 to April 2005), EMBASE (January 1974 to April 2005)等資料庫和文章的索引列表中搜尋。我們也使用手動搜尋、聯絡試驗執行者和製藥公司。

選擇標準

我們選擇有雙盲、安慰劑控制組、隨機分配的試驗,不管最後是否有外加其他治療(像是類固醇)

資料收集與分析

三個評論者獨立地挑選要納入的論文、評估試驗的品質和提取論文中的數據。

主要結論

共找到四個試驗,合計有270個病人。我們發現MX 在2年追蹤時可以減少失能的惡化(以追蹤6個月有確定失能惡化的病人比例Odds Ratios(OR) 0.3, p = 0.05)。在第1、2年不復發的比例和減低年復發率上,也得到了相似的數據。同樣得到改善的還有6個月及1年時MRI上有活性病灶的病人數目。試驗中治療組報告副作用的頻率比安慰組高。要從這些數據中得到結論必須要小心,因為這些試驗的品質和部份特質都不一致,例如各試驗間的治療的時程和病人類型都不一致。超過一半的病人來自單一個試驗,而且從我們選出的試驗沒有辦法知道長期的效果和安全性,而MX近來被陸續報導有可能會增加心毒性和白血病的風險。

作者結論

雖然是根據幾個藥物劑量和收案標準都不一樣的實驗,MX 在短期追蹤(2年)時顯示能幫助患有RR, PR, 和 SP 這幾型MS的病人減慢疾病的進程及降低復發的頻率。這幾個試驗並沒有發現重大的致癌性或是導致症狀的心毒性。然而,要更加確定這個藥物的有效性和安全性,主要是關於長期治療相關的白血病和心毒性,還需要更長期的研究。總結來說,MX有部份的效果,但是因為它長期的安全性還不明確,它應該被用來治療有逐漸失能證據、惡化中的RR 和 SP MS 的病人。

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

Mitoxantrone (MX)是一個抑制免疫的藥,普遍用在患有復發緩解型(RR), 漸進復發型(PR)和次發漸進型(SP)多發性硬化症(MS)病人身上。MS是一個慢性的中樞神經(CNS)免疫疾病,特色是會有多個區塊發炎及脫髓鞘。MS是年輕人神經功能缺損最常見的原因之一。類固醇、干擾素還有其他藥物已經被用來治療特定的症狀。這篇評論決定了MX這個廣泛被用來治療乳癌和白血病的藥,在MS的短期治療有一些療效。最常見的副作用是暫時閉經症、噁心、嘔吐、禿頭、尿道感染和暫時的白血球低下。然後解讀這些結果的時候要小心,因為這些被包含的試驗有不一致的品質和特性,不管是治療的時程或收案的病人種類都不一樣。而且,長期來說MX會造成的後果還不清楚,尤其是關於心毒性和藥物所導致白血病的風險,有愈來愈多的文獻報告這些副作用。