Cyclophosphamide for multiple sclerosis

  • Review
  • Intervention


  • L La Mantia,

  • C Milanese,

  • N Mascoli,

  • R D'Amico,

  • B Weinstock-Guttman

Dr Loredana La Mantia, Neurologist, MS Group, Istituto Nazionale Neurologico C. Besta, Via Celoria, 11, MIlano, 20133, ITALY.



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 strategy

We searched the Cochrane MS Group trials register (searched June 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3,2003), MEDLINE (January 1966 to June 2003), EMBASE (January 1988 to June 2003) 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 414 identified references, we initially selected 58; 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 favored 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 favored the control group at 24 months (0.14, CI 0.07 to 0.21). We were not able 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.

Plain language summary

Plain language summary

Cyclophosphamide (CFX) does not prevent the risk of worsening in progressive disabled multiple sclerosis (MS) patients , and major adverse effects are common.

Multiple sclerosis (MS) is a chronic disease of the nervous system affecting young and middle-aged adults. MS may be related to the immune system. Cyclophosphamide (CFX) is an immunosuppressive drug used for various autoimmune diseases. Its use for MS is controversial, as serious adverse effects are common. The data available were inadequate to attain the objectives specified for the review. We found slight evidence that CFX (intensive schedule) may slow progression in the medium-term, while some evidences might suggest worse outcomes after two years .