Cochrane review of cyclophosphamide

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Cochrane review of cyclophosphamide

Postby dignan » Mon Jan 29, 2007 9:29 am

I guess this validates cytoxan not being approved as an MS therapy.



Cyclophosphamide for multiple sclerosis.

Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002819.
La Mantia L, Milanese C, Mascoli N, D'Amico R, Weinstock-Guttman B.

BACKGROUND: 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.

OBJECTIVES: 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 2006), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3 2006), MEDLINE (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 461identified 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.

Pubmed reference
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Re: Cochrane review of cyclophosphamide

Postby Lyon » Mon Jan 29, 2007 9:58 am

dignan wrote:I guess this validates cytoxan not being approved as an MS therapy.

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.
Thanks dignan,
I was pretty excited about high dose cyclophosphamide. I guess I am pretty naive.

What about the people on high dose cyclophosphamide at Stoneybrook in New York where they seemed to be having such good results just months ago? Remember the video Ian sent of the girl bouncing around like bambi after having been in a wheelchair? 12 or 13 people with no recurrance up to, I think it was six years out?

I need to check into this further because it's going to hurt my feelings if I really was that hopeful about a complete dud.

Bob
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Postby dignan » Mon Jan 29, 2007 2:13 pm

You're excited about the high-dose cytoxan protocol, which sounds to me like it's something different than the traditional way of administering cytoxan. I'm not sure that the Cochrane group included any high dose data in their analysis. Also, don't forget this is the group that put out a study poo-pooing (sorry for using such highly technical language) copaxone in 2004 (see this thread: http://www.thisisms.com/ftopicp-1286-co ... axone#1286 ). I think from what HarryZ said way back when, the Cochrane group doesn't necessarily agree with other experts.

Have I helped salvage your battered feelings at all? I hope so.
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Postby Lyon » Mon Jan 29, 2007 2:24 pm

dignan wrote: I think from what HarryZ said way back when, the Cochrane group doesn't necessarily agree with other experts.

Have I helped salvage your battered feelings at all? I hope so.
Yes dignan you did, thank you!
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