Updated April 1, 2004
La Mantia L, Milanese C, Mascoli N, Incorvaia B, D'Amico R, Weinstock-Guttman B.
Cochrane Review Abstracts
A substantive amendment to this systematic review was last made on 02 April 2002. Cochrane reviews are regularly checked and updated if necessary.
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 CFX efficacy in patients with progressive MS.
The main objectives were to determine whether CFX slows the disease progression.
We searched the Cochrane MS Group trials register (searched November 2001), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4,2001), MEDLINE (January 1966 to ), EMBASE (January 1988 to ) and reference lists of articles. We also contacted researchers in the field.
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. Study authors were contacted for original data.
Of the 326 identified references, 80 were selected for full review, only four RCTs were selected 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) risk to 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 - 0.24 to - 0.17) and 18 months (- 0.19, 95% confidence interval - 0.24 to - 0.14). We were not able to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis).
Only limited objectives were reached. This review shows a role of CFX in the treatment of progressive MS, but less toxic schedules must be considered, before its use in the clinical practice.
La Mantia L, Milanese C, Mascoli N, Incorvaia B, D'Amico R, Weinstock-Guttman
B. Cyclophosphamide for multiple sclerosis (Cochrane Review). In: The Cochrane
Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Copyright © 2004, The Cochrane Collaboration