This Is MS Multiple Sclerosis Knowledge & Support Community

marcstck, you seem ready to investigate all possible avenues. Did you see the posts at http://www.thisisms.com/ftopicp-33633-.html. Its a long shot, but you seem to be willing to take a swing. It appears less extreme to me than the intrathecal steroids.

Dear Marcstck

Well, that's not good news. Like you I had no OB at my first LP last year and my MRI showed very few t2 spots with no inflammation.
As far as I know, in PPMS the scientists think that it's more antibodies produced by B-cells that cause the problem, not T-cells.

I have high hopes in Rituxan because it supresses B-cells although not completely. So a once a year infusion might perhaps help to slow the progression a little down. We will see the results this spring.
I have a déja-vu Did not the research for RRMS start that way?!

In a german MS forum I have read about a PPMSer who had great results with this intrathecal steroids. His was wheelchair confined 24/7 and after almost ten years of this therapy he now needs the wheelchair only for outside the house when doing long distances. Okay, that's not as spectacular as some of the results RRMSers get with the upcoming therapies but it's better than nothing.


Best
nati

Here is some research that I have found about cyclophosphamide. Not HiCy though. Seems that cyclophosphamide can have a positive effect even in PPMS when used early. I admit, that the results are not spectacular because the first article only checked efficiency for 12months and the second article showed clearly that the condition after five years had still deteriorated. I'm not sure if the patients received the cyclophosphamide during five years...:

Treatment Of Progressive Forms Of Multiple Sclerosis By Cyclophosphamide: A Cohort Study Of 490 Patients
Zephir H, de Seze J, Duhamel A, Debouverie M, Hautecoeur P, Lebrun C, Malikova I, Pelletier J, Senechal O, Vermersch P
J Neurol Sci 2004 Mar 15;218(1-2):73-7
Hopital R. Salengro, CHRU of Lille, Department of Neurology, 59037, Lille, cedex, France
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PMID# 14759636
Abstract
There are no generally effective disease-modifying drugs for Progressive forms of Multiple Sclerosis (MS). Some MS centres use Cyclophosphamide (CYC) in Secondary/Progressive (SP) forms of MS, especially after Interferon-beta-1b (INF-beta-1b) treatment failure.

Moreover, there are currently no approved drugs for Primary/Progressive (PP) MS. Using the collected data of patients with Progressive MS, we studied clinical patterns that predicted a good response to CYC treatment.

Secondly, we compared the therapeutic response of SPMS and PPMS patients to the treatment. Data from 490 MS patients were collected.

All patients presented an SP (n = 362) or PP (n = 128) form of the disease and 476 had been treated for at least one year with a monthly pulse of CYC associated with MethylPrednisolone (MP).

CYC treatment was justified because of at least a 1-point worsening on the Expanded Disability Status Scale (EDSS) during the previous year.

The EDSS score was assessed at baseline and after 6 months (M6) and 12 months (M12) of treatment.

After 12 months of CYC treatment, 78.6% of SPMS and 73.5% of PPMS patients had stabilized or had an improved EDSS score. Response to CYC was not significantly different in the two Progressive forms of MS.
Twenty-two patients presented noticeable drug side effects, one of whom withdrew from the treatment due to intolerance.

Patients with an improved EDSS at M12 had a shorter mean progressive time course (5.1 years) than patients who stabilized or worsened (7.1 years) (p = 0.02). We also observed that poor responders at M6 were also poor responders at M12 (p < 0.001).

This large cohort study showed that CYC treatment was well tolerated and suggested that a better response occurred in cases with a short progressive time course.

We did not find any difference in treatment response between the two Progressive forms of MS.

To date, no treatment is approved for PPMS and we therefore propose a trial to test the use of CYC treatment early in the course of the disease in PPMS patients with disability progression.


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#12
Treatment Of Progressive Multiple Sclerosis With Monthly Pulsed Cyclophosphamide-MethylPrednisolone: Predictive Factors Of Treatment Response
Delmont E, Chanalet S, Bourg V, Soriani MH, Chatel M, Lebrun C
Rev Neurol (Paris) 2004 Jul;160(6-7):659-65
Service de Neurologie, CHU de Nice
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PMID# 15247854
Abstract
Introduction
Cyclophospamide is used in the treatment of Progressive Multiple Sclerosis. We were looking for predictive indicators of treatment response.

Material And Methods
Forty-seven patients with Secondary Progressive Multiple Sclerosis and seven others with Primary/Progressive received monthly infusions of Cyclophosphamide (750mg/m2) and MethylPrednisolone (500mg).

During the year before Cyclophosphamide the EDSS had worsened one point in all patients with or without surimposed relapses. Evaluation was based on EDSS change at 6, 12, 24 months and 5 years.

Results
Among Secondary/Progressive patients, 91 per 100 (43/47) were stable or improved at 12 months, 65 per 100 (26/40) at 24 months and 22 per 100 (5/23) at 5 years.

Annual relapse rate decreased from 0.81 before treatment to 0.48 during treatment and 0.12 after treatment (p<0.001).

At 24 months, efficacy was correlated to a progressive phase lasting less than 5 years (p< 0.01) and to a rapid increase of EDSS of at least 2 points the year before treatment (p< 0.05).

There were no influences of age, EDSS and surimposed relapses at the beginning of treatment, and other immunoactive drugs administrated before Cyclophosphamide.

There was no significant difference in quality of response to treatment between patients with primary progressive and Secondary/Progressive Multiple Sclerosis.

Conclusion
Cyclophosphamide appears to be more efficient in early stage of Progressive Multiple Sclerosis independently of age, relapses or Neurological disability scale.

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Lyon wrote: My point is that the people at Johns Hopkins aren't saying that Revimmune won't stop the disease process in PPMS (or SPMS) because I think it's already proven that it will work stop the disease progression.
...
I don't like Accentia announcing a primary endpoint with Revimmune as a decrease in symptoms because that is a little bit more than borderline dishonesty.

Bob, there is an article from 2004 you posted in the Revimmune section here. "Interesting read form 2004". It's about ASCT and HiCy. It says that the ASCT does not work thet well when to much damage is done, or when the patient has PPMS. I tought that before ASCT the people undergo a HiCy treatment.
So if HiCy+ASCT=less effective in PPMS, why should HiCy alone be more effective?

I agree with you that if Accentia wants to get a piece of the cake they have to prove that their protocol is better than the soon coming new therapies and that it is even capable to reverse some/all disability. But this is what Campath and for some people even Tysabri already do...

I can imagine, that if the new therapies will in the trials prove to be save a possible treatment-path might be:

For "mild" RRMS: 1.FTY720
For "normal" RRMS, one or two relapses/year: 1.FTY720 or Tysabri, 2. Campath
For "agressive" RRMS: 1.Campath
For "very agressive" RRMS + SPMS: 1.HiCy

Meanwhile PPMS will ensure the jobs of the wheelchair-producers and their employees. Ha ha... I am cynical now.

best
nati

123

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Sadly, these companies don't want to risk treating SPMS and PPMS in their trials and studies because the glowing results they want to show, don't come from SPMS and PPMS patients.

One of your best Bob..