Cyclophosphamide for multiple sclerosis

  • Review
  • Intervention




Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS. We conducted a systematic review of all relevant trials, evaluating the efficacy of CFX in patients with progressive MS.


The main objective was to determine whether CFX slows the progression of MS.

Search methods

We searched the Cochrane MS Group Trials Register (June 2006), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2006), MEDLINE (PubMed)(January 1966 to June 2006), EMBASE (January 1988 to June 2006) and reference lists of articles. We also contacted researchers in the field.

Selection criteria

Randomised controlled trials (RCTs) evaluating the clinical effect of CFX treatment in patients affected by clinically definite progressive MS.
CFX had to be administered alone or in combination with adrenocorticotropic hormone (ACTH) or steroids. The comparison group had to be placebo or no treatment or the same co-intervention (ACTH or steroids)

Data collection and analysis

Two reviewers independently decided the eligibility of the study, assessed the trial quality and extracted data. We also contacted study authors for original data.

Main results

Of the 461 identified references, we initially selected 70: only four RCTs were included for the final analysis. Intensive immunosuppression with CFX (alone or associated with ACTH or prednisone) in patients with progressive MS compared to placebo or no treatment (152 participants) did not prevent the long-term (12, 18, 24 months) clinical disability progression as defined as evolution to a next step of Expanded Disability Status Scale (EDSS) score. However, the mean change in disability (final disability subtracted from the baseline) significantly favoured the treated group at 12 (effect size - 0.21, 95% confidence interval - 0.25 to -0.17) and 18 months (- 0.19, 95% confidence interval - 0.24 to - 0.14) but favoured the control group at 24 months (0.14, CI 0.07 to 0.21). We were unable to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis).

Authors' conclusions

We were unable to achieve all of the objectives specified for the review. This review shows that the overall effect of CFX (administered as intensive schedule) in the treatment of progressive MS does not support its use in clinical practice.








我們搜尋了考科藍資料庫多發性硬化群組試驗登錄(2006年6月),考科藍對照試驗登錄中心(2006年議題3), MEDLINE(1966年1月至2006年6月), EMBASE(1988年1月至2006年6月)以及文章附註的參考文章列表,並且聯繫了此領域的研究者






我們由461個參考資料先選擇了70個,最後只有4個RCT進入最後的分析,對進行性多發性硬化的病人使用密集免疫抑制藥物CFX(單獨或合併ACTH或腎上腺皮質素)和使用安慰劑組或無接受治療組比較,在12,18,24個月進行評估,發現不能預防長期失能(EDSS 進展至下一個階段)的進行,不過在12,18個月發現治療組的失能程度較輕有顯著差異,12個月時有效減輕0.21,95% CI  0.25 to −0.17, 18個月時有效減輕0.19, 95% CI  0.24 to  0.14, 不過24個月時對照組卻較佳(0.14, CI 0.07 to 0.21), 我們無法證實在其他時間的療效,有5位病人死亡,且治療期間常發生敗血症及停經(描述性研究)





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



Plain language summary

The effect of the immunosuppressive drug cyclophosphamide in people with multiple sclerosis

MS is a chronic disease of the nervous system affecting young and middle-aged adults. MS is supposed to be related to the immune system. CFX is an immunosuppressive drug used for various autoimmune diseases. As its use for MS is controversial, the Authors of this review aimed to assess CFX efficacy for patients with progressive MS. Among the pertinent literature, only five studies met the inclusion criteria of minimum methodological quality , with a total of 90 MS patients treated with CFX.
The data available were inadequate to attain all the objectives specified for the review. The Authors found poor evidence that CFX may slow progression in the medium-term. They found also that side effects such as alopecia, nausea, vomiting and menses interruption (amenorrhea) occurred at high frequency, while some evidences might suggest adverse effects also after two years .