This Is MS Multiple Sclerosis Knowledge & Support Community

The OLYMPUS Trial officially ended this month. Does anyone know why this study was extended? Was it a FDA decision? I was told today of the extension by a chief clinical investigator who said the study will not be unblinded until all results are in and that will be within a year. Anecdotally the results seem positive, so I don't get it.

I atttended the annual party/fundraiser for the Accelerate Cure Project for MS this past weekend. One of the speakers was Dr. Timothy Vollmer from the Barrow Institute of Neurology in Phoenix. He was very, very positive about the usefulness of Rituxan in MS. He didn't say anything (or at least that I recall) about the current study, just that he felt it looked like a good choice in the future. I plan to research this myself a little more. But it was nice to hear him be so positive about this drug.
Lori

Check out the video below recommended by Shayk under general discussions forum. It has great information in addition to Dr. Cohen's pathogenesis section about Rituximab by Drs. Markowitz and Cohen.


The MS Care Organization has a CME program that includes a presentation (audio/visual) by Bruce Cohen entitled Evolving Views of MS Pathogenesis.

Sorry, I could not figure out how to hyperlink it, but it's worth the trouble to view this video. Thanks for the find, Shayk!

Hello:

I have SPMS and am considering Rituxan. (This would be a Brigham and Women's Hospital). I know that initial studies show some promise for RRMS. Has anyone taken it? I wonder if it is worth the risk, because---

On 19/12/06, Biogen announced that two Lupus patients had died from PML and that 23 other cases of PML had occurred in lymphoma patients (see article below).

Can anyone suggest an article I might read on the role of B cells in SPMS?

I don't understand the logic of the protocol--two weekly eight-hour I.V.s and then more after six months. It sounds as if they want Rituxan to knock out B cells completely for a while and then let them build back up, only to knock them out again.

The most information I have found is at:

http://www.msrc.co.uk/index.cfm?fuseact ... ageid=1394

Thanks. I'm going to see if I can find the recommended film.

Hi Smiling Face and Elin

Here's a link that I think will get you to all of the presentations.

Frontiers in MS: New and Emerging Therapies

Please note these are "industry" sponsored presentations so there might be some inherent biases.

Here's a link to a list of other MS Care Consortium Presentations.

Enjoy....

Sharon

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Does anyone know if Biogen has ever published the results of the phase II trial of Rituxan in PPMS? I wonder, because I simply don't find anything about it. Or did they start right away with Phase III . I did not think this is possible...

nati

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Thanks Bob!

From a January 2008 Biogen investor presentation, they say that in the first half of 2008, they will get data from the phase 2/3 Rituxan trial in PPMS, including efficacy, time to disease progression (EDSS) over 96 weeks, safety,
and tolerability.

http://library.corporate-ir.net/library ... 010708.pdf

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Dear All,

I've been trying evaluate the risks and benefits of rituxan and found these items of interest below.

Given that rituxan has such a devastating effect on both B and T cells, I am actually surprised that only 23 cases (and 2 deaths) have been reported from PML. Rituxan seems to be rather like Cytoxin and Novantrone in nuking the entire system. At least Tysabri appears to be a more discrete weapon, acting to inhibits interactions between alpha4-integrin and its ligands (presumably stopping the migration of leucocytes to sites of inflammation within the CNS--if I understand it correctly).

I've read different estimates of PML morbidity--from 90% down to 50% die; the rest have permanent neurological damages. Treatment aims at reconstituting the immune system--discontinuing the drug, perhaps using plasma pharesis. But, no effective drug exists.

How is it that Tysabri was suspended temporarily and now strictly limited to RRMS, while rituxan can have so many cases of PML and remain in such good repute?

In addition to the reports about rituxan collected at
http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1394

you might check out


Olaf Stüve, MD; Sabine Cepok, PhD; Birte Elias, MD; Andreas Saleh, MD; Hans-Peter Hartung, MD; Bernhard Hemmer, MD; Bernd C. Kieseier, MD, "Clinical Stabilization and Effective B-Lymphocyte Depletion in the Cerebrospinal Fluid and Peripheral Blood of a Patient With Fulminant Relapsing-Remitting Multiple Sclerosis," ARCH NEUROL 62 (OCT 2005): 1620-1623. WWW.ARCHNEUROL.COM

Nancy L. Monson, PhD; Petra D. Cravens, PhD; Elliot M. Frohman, MD, PhD;
Kathleen Hawker, MD; Michael K. Racke, MD, "Effect of Rituximab on the Peripheral Blood and Cerebrospinal Fluid B Cells in Patients with Primary Progressive Multiple Sclerosis," ARCH NEUROL 62 (FEB 2005): 258-264. WWW.ARCHNEUROL.COM
258.

E Janas,* R Priest,* J I Wilde,† J H White,† and R Malhotra, "Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is crucial for calcium influx and apoptosis,” Clin Exp Immunol 139.3 (March, 2005): 439–446 at
http://www.pubmedcentral.nih.gov/articl ... id=1809325


VERY HELPFUL is the PowerPoint presentation by

Andrew Sylvester, M.D., “Rituxamab (Rituxan) and Multiple Sclerosis” at
<shortened url>


Sylvester offers charts showing how drastically both B cells and T cells are depleted, which I am unable to replicate here, unfortunately. It's sobering.

In short, is it worth taking this drug when its effect on B and T cells is so utterly destructive? What is left of the immune system? Maybe someone can explain how it is possible to live in such a state of compromise?

Thanks.



Elin

Like you, I do not understand the benefits of Rituxan over the possible immune damage and PML. It may be going forward because there is no other drug available for PPMS patients.

It is up to each of us to decide what we will take and how we are wiling to compromise our health for an uncertain result.

When I first read about PML developing in some patients given Rituxan, I knew that I would not try the drug. Some people have indicated that their doctors are planning to put them on it when it is available, which seems strange to me with its immune system depletions and PML possibility.

Recent research has shown that Tysarbi causes Interferon gamma levels to raise which produces neurotoxic effects, and yet doctors prescribe it also.

A lot of things being used to treat this disease make no sense to me.

gwa

gwa wrote:Recent research has shown that Tysarbi causes Interferon gamma levels to raise which produces neurotoxic effects, and yet doctors prescribe it also.

A lot of things being used to treat this disease make no sense to me.

Holy brains Batman! That just sounded too far out so I had to look it up myself. An MS med that increases Ifn-gamma, a cytokine which is known to worsen MS.

Induction of systemic TNFalpha in Natalizumab-treated multiple sclerosis.
Eur J Neurol. 2008 Jan 9

The mRNA expression of eight different cytokines in peripheral blood mononuclear cells in 19 individuals with multiple sclerosis was determined at baseline and after 6 months of open-label treatment with natalizumab. Cellular expression of tumor necrosis factor alpha (TNFalpha) mRNA and number of cells secreting TNFalpha and interferon gamma protein significantly increased over the 6 months. Kurtzke EDSS scores improved because of the resolution of relapses, but not fatigue severity scores. The observed increases in systemic proinflammatory cytokines by natalizumab treatment are discussed in relation to fatigue and systemic immunity.

NHE

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