CRABs dont slow EDSS progression - 3 studies

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CRABs dont slow EDSS progression - 3 studies

Postby Frank » Tue Jul 13, 2010 9:58 am

Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby swynjones » Tue Jul 13, 2010 12:18 pm

Embry makes some valid points here regarding the need for an open and thorough look at CCSVI.

But ultimately this article is a little bit hypocritical because he criticises the CRABS due to 3 studies which have not demonstrated clear efficacy in reducing disease progression. But importantly the CRABS have been put through clinical trials and proven to reduce relapse rates, and improve quality of life.

Whereas on the other hand no clinical trial of any substantial note that I am aware of has demonstrated any reduction in disability progression or any significant effect on relapse rate with the best bet diet which Embry promotes and from which I would imagine he himself has made money through his book sales.

Have to say it is rather annoying the anti-drug industry stance. Getting any drug approved is incredibly difficult. Lengthy, costly and stringent clinical trials are necessary which are verified independently. Whereas anybody can suggest a dietary supplement or protocol based on an un-proven theory and not receive the same critical analysis.

Yes I do work in the drug industry. But the company I work for is not active in MS research. I work in the cancer research area and I know how hard everyone arounds me works to find that drug target that is going to make a different to patients and improve cancer survival rates. I am 100% certain therefore that it is the same at those drug companies who do work in the MS area.

MY wife has MS, hence my interest in reading this forum and following MS research.
Last edited by swynjones on Tue Jul 13, 2010 12:20 pm, edited 1 time in total.
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Postby scorpion » Tue Jul 13, 2010 12:19 pm

Let me guess Dr. Ashton Embry. Yep I was right!!!!!! ha!
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Postby Frank » Tue Jul 13, 2010 3:14 pm

@swynjones: While the article does suggest to promote CCSVI I think the major point - and the point that I wanted to bring up here - is that the CRABs do not improve EDSS progression.

Accepting that conclusion its imo. highly questionable whether its justified to spend that amount of money (like 15.000 EUR per year) for the given benefit profile.

While relapses are a hassle I'm pretty sure that many MS patients would be reluctant using these daily injections with side effects if I they had to acknowledge that they will not make a difference on their long term disability outcome.

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby swynjones » Tue Jul 13, 2010 11:17 pm

Frank wrote:@swynjones: While the article does suggest to promote CCSVI I think the major point - and the point that I wanted to bring up here - is that the CRABs do not improve EDSS progression.

Accepting that conclusion its imo. highly questionable whether its justified to spend that amount of money (like 15.000 EUR per year) for the given benefit profile.

While relapses are a hassle I'm pretty sure that many MS patients would be reluctant using these daily injections with side effects if I they had to acknowledge that they will not make a difference on their long term disability outcome.

--Frank


I agree these studies raise some questions, and ive not looked at them in detail. But I do know that the NHS study is a retrospective look at how patients did with disability progression. And the problem with the data is that its not controlled in the way a clinical trial would look at this. For example, one reason the NHS study may have found no difference in disease progression between those on CRABS and those who didnt take drugs might have been because those who decided not to take drugs were mostly made up of people who had a milder form of MS and therefore were relunctant to take any medication that would involve injections and give them flu symptoms. On the other hand those patients who were on the CRABS over 10 years or so were more likely to be those patients with more progressive forms of MS where their neurologist felt it important they were on the meds.

So I think it quite likely the NHS study is not comparing like with like. Clinical trial would be ensuring that patients were randomised to placebo or CRAB and therefore you would expect both groups to contain equal numbers of patients who had milder MS and equal numbers of patienrts with more progressive MS. But that's not the case with the NHS data.

Also hae to remember that there are a lot of publications out there which have shown reduction in disease progression so....

But I agree these studies raise questions. My wife is not on nay CRAB at the moment, but we need to make that decision. She has had MS for 5 years, seems to be doing ok. And its a really hard decision to take something that will make her feel more tired probably and feel pretty rough, particularly if the long-term benefit isnt going to be there.
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Postby Frank » Wed Jul 14, 2010 3:00 am

Your point about the difference between controlled clinical trials and retrospective analysis is basically valid. But I think there is no better data out there. The CRABs where approved by primary endpoints of MRI lesions and relapse rate which is not a valid indicator for EDSS progression over time.
And other trials you mentioned that looked into EDSS progression over time are pretty small and short term and they do show conflicting outcomes - so I dont regard their data being superior to the retrospective analysis - maybe you know about some other trials than I do, if so it would be nice of you if you could provide a link to them.

Regarding your assertion that those who stay on CRABs are the more severe cases while the ones doing better tend to drop out of treatment seems questionable to me.

I would rather suggest the opposite:
If you got MS your neuro (at least here in Germany) will strongly recommend you to some of the CRABs. Those who are doing well in the consecutive years after starting the drug will imo. certainly not discontinue to use it because they (and certainly their neuro) will attribute the success to the use of the drug.
On the other hand those with less success might be advised to escalation therapy like Mitoxantrone.

One imo. specially flawed study comes from Teva Aventis. They looked at the long term (they got far more then 10yrs data) development of relapse rate of Copaxone users and they published that (i think it was) in year 10 that the relapse rate dropped to 0.2/year while it started (I guess it was) 0.8/year.
The flawed point is that the study population has significantly decreased.
So it seems obvious to me that only the people that did very well on Copaxone, (or what seems more likely to me) people who have a naturally benign course stayed in the trial, while people with less benefit dropped out of the trial to switch to maybe an other one of the CRABs. Maybe even Teva suggested the ones that did not "well enough" to leave the trial (try something else that might better help in your individual MS case) to get better data.

I'm far from being a conspiracy supporter but this business is about serious money and earning money is the primary effort also for drug companies.

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby sbr487 » Wed Jul 14, 2010 3:44 am

swynjones wrote:from which I would imagine he himself has made money through his book sales.


Dr.Embry is backing CCSVI and has has made donations for CCSVI study, which if turns out be effective can put him out of business. That speaks volumes about his money making agenda.

Have to say it is rather annoying the anti-drug industry stance. Getting any drug approved is incredibly difficult.


There is no doubt pharma does do good work when it comes to treatment. But cant say much about cure. CAn you give some examples.
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Postby swynjones » Wed Jul 14, 2010 5:47 am

sbr487 wrote:
swynjones wrote:from which I would imagine he himself has made money through his book sales.


Dr.Embry is backing CCSVI and has has made donations for CCSVI study, which if turns out be effective can put him out of business. That speaks volumes about his money making agenda.


Have to say it is rather annoying the anti-drug industry stance. Getting any drug approved is incredibly difficult.


There is no doubt pharma does do good work when it comes to treatment. But cant say much about cure. CAn you give some examples.

I'm not really saying he's in it for the money, I'm not that cynical. But if CCSVI is proven I would think that would fit nicely with Embry's BBD theory anyway. If BBD is effective then this would perhaps be indicative of MS having a systemic vascular component. So dont agree that it would put him out of business. More likely that CCSVI and BBD would be combined as a treatment, cos they would both be supporting MS as being a vascular condition.

My issue with Embry's article is that at the end of the day here he is being critical of the MS drugs. But there is zero scientifically proven evidence that his BBD has any effect on 1.disease progression or 2.relapse rate.

There was a small trial started in 2006 on BBD, and they were due to publish in 2008. But the data stil hasnt been published. Why is this? Surely not because the trial showed no effect on disease progression or relapse rate???

So that's why I find it hypocritical.

2 treatments.

1. A diet with no scientific evidence behind it to suggest it does anything at all.
2. Drugs that reduce relapse rate but perhaps dont impact long-term disease progression.

Now it seems these long-term studies on the CRABS raise some serious questions about long-term disease progression efficacy. But it is important to remember the drugs are marketed primarily on the back of reducing relpase rates, whcih scientifically theyve been proven to do.

So to me it jsut seems a bit rich for Embry to be critisicing the CRABS when theyve been proven to be of benefit, whereas the BBD he promotes has no proven benefit.


Regarding drug cures you are right. Pharma industry has massively disapointed in this regard. It was beleived that cracking the human genome would lead to better more effective treatments, and cures. But this as largely not happened.

On the whole chronic disease isnt cured but is delayed long enough so that the patient dies of something else. Good example of this is how we manage diabetes. Chances are that this is where MS will get to, eventually for most people it will be managed well enough through disease modifying drugs and symptom management that people die of heart attacks and strokes before the MS gets that severe.

Same with majority of cancer drugs, they arent cures in most cases but they increase survival time, by say 6 months or a couple of years.

However, having said that there are cures. Childhood leukaemia's are often cured. There are lot of women who've had Herceptin breast cancer treatment and combined with chemo the disease is in remission, and lot of women now who 10 years on from initial breast cancer diagnosis are still free of disease. Similarly, with men and prostate cancer.

Are these cures, or just delaying disease from coming back?
Last edited by swynjones on Wed Jul 14, 2010 5:55 am, edited 2 times in total.
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Postby swynjones » Wed Jul 14, 2010 5:52 am

Frank wrote:Your point about the difference between controlled clinical trials and retrospective analysis is basically valid. But I think there is no better data out there. The CRABs where approved by primary endpoints of MRI lesions and relapse rate which is not a valid indicator for EDSS progression over time.
And other trials you mentioned that looked into EDSS progression over time are pretty small and short term and they do show conflicting outcomes - so I dont regard their data being superior to the retrospective analysis - maybe you know about some other trials than I do, if so it would be nice of you if you could provide a link to them.

Regarding your assertion that those who stay on CRABs are the more severe cases while the ones doing better tend to drop out of treatment seems questionable to me.

I would rather suggest the opposite:
If you got MS your neuro (at least here in Germany) will strongly recommend you to some of the CRABs. Those who are doing well in the consecutive years after starting the drug will imo. certainly not discontinue to use it because they (and certainly their neuro) will attribute the success to the use of the drug.
On the other hand those with less success might be advised to escalation therapy like Mitoxantrone.

One imo. specially flawed study comes from Teva Aventis. They looked at the long term (they got far more then 10yrs data) development of relapse rate of Copaxone users and they published that (i think it was) in year 10 that the relapse rate dropped to 0.2/year while it started (I guess it was) 0.8/year.
The flawed point is that the study population has significantly decreased.
So it seems obvious to me that only the people that did very well on Copaxone, (or what seems more likely to me) people who have a naturally benign course stayed in the trial, while people with less benefit dropped out of the trial to switch to maybe an other one of the CRABs. Maybe even Teva suggested the ones that did not "well enough" to leave the trial (try something else that might better help in your individual MS case) to get better data.

I'm far from being a conspiracy supporter but this business is about serious money and earning money is the primary effort also for drug companies.

--Frank


Frank. I take your point about the Teva data. I agree I felt it was a claim they couldnt make because of the point you made about people staying on Copaxone if the drug was working for them (could jsut be those with a more benign MS), and coming off the drugs if they arent working (could just be people with more progressive MS).

I think the NHS data regarding the patient populations could be argued either way. Maybe you are right. But my point was that we dont really know if we are comparing like with like in this data-set. And so the data is flawed from this viewpoint and needs to be interpretated with care.

I will see if I can dig out some EDSS progression plots from some papers showing efefctiveness of different CRABS. there is stuff out there that has been peer-reviewed, albeit from smaller patient numbers.
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Postby sbr487 » Wed Jul 14, 2010 6:14 am

Regarding drug cures you are right. Pharma industry has massively disapointed in this regard.

I think I would use the word disappointed if they did not do what they were expected to. I think capitalist world, do you think someone who comes up with a cure would get a pat on his back or will be cold shouldered. I think Dr. Steinman thinks that a BP drug can help MS but he is not getting funding for trials. Well, who would be interested in putting their own drugs out of business.

It was beleived that cracking the human genome would lead to better more effective treatments, and cures. But this as largely not happened.


Do you know that no major pharma is interested in this area and one doing research is a charity org in UK. Of course, it would have been good if that Dr. venter spent some time in genetic cures rather than trying some fancy "life in the lab stuff". I am not saying that it is not important but whether is it so pressing at this time?
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Postby HarryZ » Wed Jul 14, 2010 7:20 am

Have to say it is rather annoying the anti-drug industry stance. Getting any drug approved is incredibly difficult. Lengthy, costly and stringent clinical trials are necessary which are verified independently. Whereas anybody can suggest a dietary supplement or protocol based on an un-proven theory and not receive the same critical analysis.


The MS drug industry has brought a lot of this criticism upon themselves. The marketing wars, expensive trials comparing one CRAB to another and continued escalating drug costs are but part of it. 3 of the CRABs have Orphan Drug Status still behind them yet their cost has gone up continuously since their inception. And because they have gone up, the people who make Tysabri have raised the wholesale cost of the drug from its original cost of about $ 1800 an infusion to now over $ 3,000 in 5 years!!

And as we see, the long term benefits of the CRABs are highly questionable and their results (who writes the reports) are all over the map.

If you look at Copaxone's history, you will see that its initial trials did not reach significant statistical results over placebo. This was devastating so the makers revisited the data, dredged it and manipulated it and finally were able to get results just over the the acceptable level for approval. We saw what the independent Cochrane Group wrote about Copaxone...useless in the treatment of MS yet 10 year data published by Teva says its great! What's the MS patient and doc to believe?

This kind of debate over the CRABs will go on forever and we will always be shown data by the makers that their drug works and is better than the next guy's. The revenue associated with these drugs is too huge to allow a slip in marketing share and every tactic will be used to keep that share as high as possible.

This is the way most pharmaceutical companies operate and is a fact of life. It's also a fact that it's all about the money and little, if anything, to do with the health of MS patients.

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Postby Thomas » Wed Jul 14, 2010 8:08 am

swynjones wrote:My issue with Embry's article is that at the end of the day here he is being critical of the MS drugs. But there is zero scientifically proven evidence that his BBD has any effect on 1.disease progression or 2.relapse rate.


This seems like a perfect example of an Ad Hominem Tu Quoque fallacy. "Because there is no proof for BBD, his views on CRABS must be wrong."

Description of Ad Hominem Tu Quoque

This fallacy is committed when it is concluded that a person's claim is false because 1) it is inconsistent with something else a person has said or 2) what a person says is inconsistent with her actions. This type of "argument" has the following form:

1. Person A makes claim X.
2. Person B asserts that A's actions or past claims are inconsistent with the truth of claim X.
3. Therefore X is false.

The fact that a person makes inconsistent claims does not make any particular claim he makes false (although of any pair of inconsistent claims only one can be true - but both can be false). Also, the fact that a person's claims are not consistent with his actions might indicate that the person is a hypocrite but this does not prove his claims are false.

http://bit.ly/158Dgh
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Postby swynjones » Wed Jul 14, 2010 8:55 am

Thomas wrote:
swynjones wrote:My issue with Embry's article is that at the end of the day here he is being critical of the MS drugs. But there is zero scientifically proven evidence that his BBD has any effect on 1.disease progression or 2.relapse rate.


This seems like a perfect example of an Ad Hominem Tu Quoque fallacy. "Because there is no proof for BBD, his views on CRABS must be wrong."

Description of Ad Hominem Tu Quoque

This fallacy is committed when it is concluded that a person's claim is false because 1) it is inconsistent with something else a person has said or 2) what a person says is inconsistent with her actions. This type of "argument" has the following form:

1. Person A makes claim X.
2. Person B asserts that A's actions or past claims are inconsistent with the truth of claim X.
3. Therefore X is false.

The fact that a person makes inconsistent claims does not make any particular claim he makes false (although of any pair of inconsistent claims only one can be true - but both can be false). Also, the fact that a person's claims are not consistent with his actions might indicate that the person is a hypocrite but this does not prove his claims are false.

http://bit.ly/158Dgh


I'm sorry but it is not a perfect example of that at all. if you read what I wrote I started by saying Embry makes some valid points regarding the CRABS and the questions we should be asking about their long-term benefit and disease progression. Where he is not right is to be completely dismissive of the CRABS because they have been proven to reduce relapse rates.

I am not quite sure why you disagree with what I have written. I agree with questioning the long-term efficacy of CRABS on disease progression. I agree with fully investigating CCSVI. But I disagree with the tone of Embry's article which is CRABS are bad and CCSVI treatment is good because if we look at where the scientifically proven evidence is we find it supports CRABS for relpase rate but provides no such support for CCSVI or BBD. Now we may well be looking at a different scenario 5-10 years down the line where first-line treatment is stent/balloon angioplasty for some MS patients. Which is why I support research into CCSVI and would support a clinical trial to fully test out this theory.
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Postby cheerleader » Wed Jul 14, 2010 10:18 am

Actually--CCSVI has been a tough one for Dr. Embry, and he'd be the first to admit it. He's been in MS research for many years now, and has held a firm belief in the autoimmune model- as evidenced by the research he's funded. His Best Bet Diet was based on removing foods that activated an immune response in the body. And the vitamin D research was looking at immune modulation as well. We debated CCSVI for many months, but he's read all the research, met all the doctors and seen the patients before and after angioplasty.

Yes, CRABS do stop relapses. That's why Jeff has remained on Copaxone after his angioplasty for double jugular stenosis. I believe they have a part to play in recovery from venous congestion, especially since we do not know how long the immune system remains active after blood flow is corrected...but CRABS do NOT slow progression.

The only documented physical correlation to MS disability shown in MS brains has been iron deposition as evidenced on SWI-MRI (Haacke/Zivadinov/Bakshi). There is no linkage in white matter lesions and disability. period. So, there is an underlying mechanism which is destroying gray matter in MS brains, despite a halting of white matter lesions by CRABS. What is killing the gray matter? Some say iron deposition created by extracranial stenosis, some say the axons are degenerating due to some as yet unknown cause. Me--I believe it's hypoxic injury due to slowed perfusion. Whatever is destroying gray matter---the CRABS are not addressing it. And patients deserve to know this.
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dx dual jugular vein stenosis (CCSVI) 4/09
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Postby Perkele » Wed Jul 14, 2010 2:07 pm

cheerleader wrote:The only documented physical correlation to MS disability shown in MS brains has been iron deposition as evidenced on SWI-MRI (Haacke/Zivadinov/Bakshi).

What about this one:

"UCSF researchers have identified a correlation between higher levels of glutamate, which occurs naturally in the brain as a byproduct of metabolism, and greater disease burden in multiple sclerosis patients."

"This is the first time that we have had the ability to measure glutamate toxicity in the brain in real time, which gives us a marker for monitoring disease progression as well as our treatment of the disease," said Daniel Pelletier, MD, study author, associate professor of neurology and a member of the Multiple Sclerosis Research Group at the University of California, San Francisco."

Read the whole article: http://www.prweb.com/releases/UCSF_Glut ... 367794.htm

In the neuro community (ECTRIMS) there has been quite some time the acceptance that the best correlation to MS disability is the grey matter loss.

-PERKELE
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