This Is MS Multiple Sclerosis Community: Knowledge & Support

If you go back and look at the trials with the CRAB's you will see that Betaseron, the first approved drug, was trialed randomly on all kinds of MS patients. There was no such classification of RR, PP, SP etc. that existed at that time. Results...about 30% effectiveness over placebo.

Along came Avonex and they were able to carefully pick their RR trial patients from the newly established classification scenario. They had to ensure that their results were as good as or better than Betaseron so they would get the coveted Orphan Drug Status rating. Guess what?.....about 30% benefit.

Next came Copaxone. Same idea but the first trial showed such poor results that they didn't reach statistical significance. They ran another trial, dredged the data to the ultimate and barely got to the 30% effective level....and of course got Orphan Drug status.

Not sure about Rebif but the same result of about 30% over placebo.

Seem strange that all 4 drugs rate themselves at about 30% efficacy over placebo?! These results prompted Dr. P.O. Behan's Pathogenesis of MS paper where he stated that a 30% effective rate of these drugs was suspiciously the same as the placebo effect in trials.

Kind of makes you wonder about them, especially when they cost and arm and a leg and their price continues to rise every year!

Harry

Beyond study:
"Patients in the study were required to exhibit clinical signs of the disease in the past year before entering the trial. When compared to the relapse rate during the year prior to study enrollment, Betaferon® 250 mcg reduced the relapse rate by 78 percent during the observational period which was up to 3.5 years (Betaferon® 500 mcg: 79 percent, Copaxone® 79 percent)."

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At least one of the companies must be liars - but who the fuck is it?

I am rather reluctant to believe any figures published by the pharma...

ursula

Hi harry,

that´s exactly what my neuro said to me - he is working in a (independent!!) ms research group, too.

ursula

I disagree with elements of both of the aove posts. I agree that statistics can absolutely be manipulated. 78%,67%,57%, 49% whatever. In a large statistical sample Tysabri is absolutely effective in reducing relapses and reduing MR progression. Is it 100% effective, or does it work for everyone and is it perfectly safe? Heck no, otherwise everyone would be on it and we wouldn't behaving these conversations.

As someone living with MS for the last 15 years and with a masters Degree and a practicing physician's assistant treating people with MS I see, on a daily basis, Tysabri's effects. Again, I understand that this is a general statement and not everyone will derive the same benefits from it, but given approved therapies for MS it is the most effective proven MS therapy and after Copaxone, it is probably the safest.

Multiple studies (noted excellently by HArry) ahave shoen ABCRs to be about 30% effective and all have the undesirable effect of having to be administered by injection, so of course it makes sense that may of the trials try to make their drug "better" or "more effective than the next, even though they are splitting hairs. The thing though more than numbers that should be taken from the BEYOND and BENEFIT trials is not how effective or ineffective the ABCRs are but that EARLY TREATMENT is absolutely critical in terms of preventing and slowing the disabling effects of MS.

How do you know this? If your neuro says that you or someone you love is CP SP RP or PP and would not be a candidate for Tysabri because its not idicated and that something like Beta i, that is the biggest bunch of crap. That is what you should be suspicious of and not Biogen's PR department. There is no available way of telling if someone falls into these categories. These diagnosis are made clinically. Reading the fine print Tysabri is "generally" not indicated as initial therapy. It is insane though that people need to get worse before getting the better treatment, this is especially the case with insurance companies.

From strictly a logic point EVERYBODY is SP after their attack and they have had an insult to their CNS, because that damage iris irreversible. Even if someone is no longer having "attacks" there is no way to tell if there is not T Cell activity causing further neuro degeneration and even 3T scans cant discern subtle changes . T

The paradigm that most neuros have is if you're SP you get put on Beta because they have the indication for SP and this is why Avonex and Rebiff are trying to get the same indications. Once this happens the whole which 30% effective argument starts all over again for people with so called "SP." Think about the similarities of all the data on the ABCRs. Someone is absolutely lying when all of a sudden it is said that an ABCR is 7o something after multiple studies clearly do not support such a wild claim.

Most research neuros are in bed with companies they do research for and are afraid to prescribe Tysabi or even think out of the boxand would rather continue to perpetuate this old MS treatment paradigm the the goal of treatment is slowing progression when it should be doing everything possible to stop it completely.

Correct me if I am wrong, but with the "results" coming in at 30% OVER placebo, that would mean they are NOT "the same as the placebo effect in trials"? I don't know the actual maths (or the lack thereof ) in the statistics, but would that not make them approach something like 30% for placebo & 50% for the CRAB? Your post seems to try to imply the CRABS only achieved 30%, in total.

Personally, I was once on Rebif, and I do not see how in the world you could not tell, you were not on the placebo; and therefore "placebo" becomes theoretical. I am FAR from a CRABS fan, trust me.

Hi.

Assuming that the trial results were not altered and reflect the reality itself, I insist that they compared the relapse rate of the treated group with the relapse rate of the placebo group.

Here is my question: how effective is Tysabri when taken by patients not belonging to the demographic group of the trials?

It has never been tested with people having progressive MS. Progressive MS has a different mechanism of damage to nervous tissue. How do we know that it does not make them worse, somehow? It could violate the fundamental principle of "Primum non nocere".

In example, the use of corticosteroids is not officially approved for MS. As this study shows, their use could be detrimental by accelerating the neurodegenerative part of the disease through the induction of neuronal apoptosis:

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How sure can we be that Tysabri won't make neurodegeneration worse? Messing up with the integrins is not a good thing to do. Preventing the immune system from leaving the blood vessels is an invitation for trouble.

On the other hand, leaving MS untreated is an invitation for trouble, too. It 's up to the individual to take the decision. But it has to be an informed one. How informed can a decision based on trial data from patients with a completely "ideal" disease status be?

sou

_________________
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."

Cure,

Initially, I had the same kind of question you did about placebo. I then read Behan's Pathogenesis of MS. I have quoted but a small section of it relating to this area.

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Of extreme importance is the caveat of Steiner and Wirguin that ‘all three studies report a very similar reduction (around 30%) in the relapse rate’.2 They highlight that ‘the almost identical results of clinical trials using different agents, and their inability to go beyond the 33% line, raise the possibility that the entire observed benefit is only a placebo effect, and that the significant deviation from the true placebo might be the outcome of partial unblinding of patients by the side-effects’.2 Similar results were found by Calabresi where improvement with ß1a-interferon was precisely 33%.102

In a recent review of the possible benefits of interferon in relapsing-remitting MS, The Cochrane Review drew attention to 208 articles of which only seven met all the selection criteria and formed the subject of their conclusions.11 The variable quality of the trials, the inadequate methodology, the very high proportion and incomplete description of drop-outs, and the failure to adhere to the strict original intentions of the trial detract seriously from any claims that were made.11 These trials
should be considered as single- rather than double-blind. They drew attention to the fact that if interferon-treated patients who had been removed from the study were deemed to have worsened, the significance of the reported effects was therefore lost. The efficacy of interferon on
both exacerbations and on progression of the disease was modest after one to two years.11

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Reading the entire paper makes one wonder just how the researchers have come up the kind of results they did over the years. Basically Behan stated that they have been working with an unproven hypothesis for decades and continue to base their trial data on this information. I tried to find a link on the net for this paper but was unsuccessful. I would be glad to e-mail it to you if you want.

Harry

Yeb,

And the Tysabri researchers at Biogen are any different? The drug was trialed with mild case MS patients. The results were wonderful, according to Biogen. While I agree we should be looking to do everything possible to stop the progression of the disease, my opinion is that Tysabri is not much different than the CRABs when it comes to the overall effectiveness against disease progression. Perhaps my opinion will be proven wrong over time or perhaps Tysabri will eventually get pulled as being too risky. But at least the varied opinions in this thread make for interesting reading and sharing.

Take care.

Harry

You put that very well. I just think in terms of treating MS there is not a lot of room for letting up on the disease, just becuase there is so little we have had to treat it up until this point.
MS is scary, but this kind of thinking is scary too, in my opinion. Tysabri's MOA specifically blocks T cell transmission. Yes it has risks but for me the risks are outweighed by its advantages.

No Tysabri's researchers are no different. They like all the ABCRs are trying to sell a very expensive medication to patients with a disease state that there is not lots of treatment options available. The difference is that their drug is seemingly not only more effective but also a better tolerated medication (non injectable) otherwise it wouldn;t have been fast tracked when it was.

I am not trying to be the #1 Tysabri cheerleader, but there is much much mis information on it and other meds and treatment options for MS. THe MS medical community as a whole is who is resposible for much of this for the reasons outlined in my last post.

Yes, there is mis-information out there about all the MS meds and a lot of that comes from the very companies who manufacture them. Just look at the head-to-head trials that have been done with the CRABs as well as long term trial data that these companies put out and you quickly start to wonder just who is telling the truth or simply interpreting their data to make it sound like "their" medication is better than the competitor's!

Can you imagine the cost of doing these additional trials? But one can understand why they do them because a couple percent shift in the MS drug market translates into millions of dollars of extra revenue.

I've corresponded with a couple of people who are involved in MS research and they tell me that from a theory point of view, the potential problems with Tysabri are huge. Add that to the poor reputation that Biogen has within the MS world of medicine and you can perhaps understand my concern to MS patients in the long term. Let's hope these concerns prove unfounded...MS patients don't need more problems.

Harry

Hi.



No, it does not do it so "specifically". Here is an expression profile of the tissues where the protein subunit Tysabri attaches to are expressed:

http://www.ncbi.nlm.nih.gov/UniGene/EST ... =Hs.440955

It is hugely expressed at the Thymus, spleen and the bone marrow, but there are several other important places.

My biggest concerns about Tysabri have to do with cancer. A mutation that could lead to a tumor in 20 years will not be arrested from the immune system in time if it is blocked in the vessels.

Tysabri is not as specific as it should be. It not only blocks Th lymphocytes. It could very well block other immune cells and interfere with the functionality of a4-b-integrin at the other tissues throughout the body.

My 2 cents. I am far from an expert but thinking about blocking the integrins makes me feel very insecure.

sou

_________________
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."

I do work with many patients with MS. I see the effects Tysabri has. PAtiennts that were coming into the office 2-4x per year with attacks are no longer having multiple attacks per year. I have even seen some, i emphasize some patients have sligh improvements in their EDSS scores. I know that this is just my experience, which I am sharing what I have seen in the 250 or so patients with MS I see.

My big 2 cents on the issue is, that all things being equal, the small "potential" risks concerning Tysabri are out weighed by the REALITY of the BIGGER risks of untreated or under treated MS. Argue about the MOAs, the ethics of pharmaceuticals or potential for some catastrophic side effect, but lets not lose sight of the disabling nature of MS.

Personally, I would rather use Tysabri than risk under treating my MS, because while I nor anyone may know that ultimate long term risks of Tysabri are I think everyone knows what the outcome of under treating MS means in the long run.

pat

I'm just starting to come to grips with the fact that improvements in EDSS are more of an ideal. When I got in the Tovaxin trial, I was just sure I was going to "get better". That didn't seem too far fetched because MS had really just started messing with me and I went from .5 on EDSS to 4 in about two years. Now that I've had two Ty infusions, I don't feel like I'm spiraling downwards out of control like I did during the trial. That is great relief, but when real (by that I mean more than just an inconvenience, but life changing) MS symptoms are new to you, it's a point you must deal with and accept. I don't want to be stuck where I'm at now since I am so limited in what I can do. It's like by the time I walk outside with the intent of doing some small amount of work, I'm too wobbly and weak to do it. That's a bummer. But a very short time ago I was at the point where I wouldn't have been able to even try to do something like work outside. I just didn't have it in me. I have no idea how I've kept my job through all of this; I'm lucky my job is not physical save for some walking.

But at any rate, that's what Ty has done for me so far. The jury is still out since I just started (I get my third infusion on 1/7), but I'm slowly accepting that this is what I'm going to have to deal with, but just a few months ago, I was without hope. And that is a shitty place to be. This post doesn't really go with the rest of the thread, but I thought I'd chime in as to why I take it despite the risks. It is what I'm hoping allows me to live a bit of life, not just stay breathing and looking out through a prism of despair. So, for now anyways, I feel like it's allowed me to put a little of the onus back on me. I suspect Ty has really slowed my progression down to where I can possibly start exercising again and try and get some range of motion back. At least that's a somewhat better place to be than in the middle of constant progression where you don't even want to open your eyes or move your head for fear you will fall or tip over. Basically I just don't feel as 'fragile' as I have been feeling. I hope that makes sense because I wanted to put in words what this drug 'feels' like for one patient anyway. I don't actively 'feel' it, but I am slowly feeling more stable and solid. So I think the potential reward outweighs the risk simply because just surviving and maintaining sinus rhythm is not what any of us want. We want to smile and laugh and live and love, and that's very hard when you're progressing fast.

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http://myhopefuljourneyintoactualmsreco ... ogspot.com

Thank you for that post. I am sorry to learn that you were on the Tovaxin trial. Ultimately, its concept is great, but its application is far from refined...This is why I think no one with the MS should tral a med, no matter how promising it may be, just because it is an unknown, and many of us with t he MS can not afford to loose ground neurologically.

The best time to start Tysabri is before you start seeing disability or the EDDS sliding. Tysabri fundementally doesn't "fix" anything, but I think once the chronic inflamation within the CNS is slowed it can function much better.

I am so glad to hear that you have seen those improvements. The goal now is to hold steady until neuro regeneration or remylination comes.

amen

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