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Tysabri: Fine Young Cannibal or CRAB's New Partner in Crime

Posted: Sat Dec 04, 2004 10:35 pm
by rndlph
I would like to hear some discussion on the possible meaning of the one-year SENTINEL trial information that was recently released. Right now, I am leaning toward pushing for combination therapy when I make the leap to Tysabri. But I would really like to be talked out of continuing the Avonex. The side effects have eased this past month (after a year on treatment), but it still feels as though I am playing Russian Roulette with my Sundays every Saturday night. Of course, the game gets even more serious when I think about Avonex's purported effects on brain atrophy.

I think SENTINEL does establish an independent method of action, but I see the results as somewhat equivocal with respect to actually using the drugs in combination. Am I being stupid to compare the mean relapse rates between SENTINEL and AFFIRM? I just have this overwhelming that Avonex's efficacy is insignificant.

Any predictions on how insurance carriers will react to combination therapy? What about combination with the other CRABs?



Posted: Sun Dec 05, 2004 7:18 am
by MeadowStream

Both trials show Tysabri to be the big difference maker. I suspect that if you do not have antibodies to Tysabri then monotherapy is the way to go. The mechanism of action seems to suggest that the longer you take Tysabri the better the results. What does your neurologist say?


Posted: Sun Dec 05, 2004 9:21 pm
by rndlph

I will not see my neurologist until after the holidays, so I don't yet know what she thinks. It should be interesting. She believes in aggressive treatment.

Your take on combination therapy seems similar to mine. I just wonder what result Biogen was hoping to see in SENTINEL. I mean, would they like to see a narrower differentiation between combination and Avonex. It clearly establishes the independent mode of action, but don't they have to compare across the two studies to make a definitive case for combination? If they are doing this, it sounds like a loser at this point to me. This must be part of their design from the outset. Too bad for Biogen, but I think they will survive. Tysabri is poised to dominate the entire market, not just Avonex's part of it.

Of course, Avonex has a longer history, is a more proven therapy. It just seems to be proven even more mediocre in this latest round of results.

I was struck by your comment that the longer you take Tysabri, the better. I like the sound of that, but why do you think this to be the case?

Anyway, I guess Tysabri is a cannibal. And sometimes I feel like its missionary. Now if I can only find the keys to this boat, my troubles would be over.


Mechanism of action

Posted: Tue Dec 07, 2004 3:44 am
by MeadowStream

The reason the longer you take it the better the results MAY be is that natalizumab works by binding to the VLA-4 activating site and does not allow T cells to cross the BBB. It cannot do anything about T cells that are already across and causing damage - but those will eventually die off. When they have died off, and with few or no new T cells crossing BBB, then neural regeneration can occur to some extent and new damage will hopefully not occur.

I think BiogenIdec was hoping that 1+1 would equal 3 or 4. There is a school of thought that beta interferons help shore up the BBB and if this is the case then Tysabri just does a much better job of locking the door.


Re: Tysabri: Fine Young Cannibal or CRAB's New Partner in Cr

Posted: Fri Dec 10, 2004 7:01 am
by HarryZ

You have a difficult decision to make as do many other MS patients in your situation.

Tysabri is just out of the starting gate and Biogen's data shows that it is better by itself than it is in combination with Avonex. I always like to think that the fewer drugs MS patients have to take the better off they will be in the long run. You mentioned that your neuro likes to take an aggressive approach to MS....I hope she places more emphasis on treating the patient as opposed to simply treating the disease. After all, you are the one that has to deal with any possible side effects.

Some neuros are starting to ask questions about the data on Tysabri. If you check the link that I posted in the other thread you can see that interpreting data from clinical trials can be quite a challenge. My opinion, which everyone knows here, is a lot of caution but each person has to make up their own mind on how they want to proceed. I also suggest you sit down with your neuro and discuss all the aspects you have concerns about and insist that she take the time and go over everything with you. Make a decision you feel comfortable with since you are the one who is living with this disease.

Whatever decision you eventually make I hope it works out well for your overall health.


Posted: Mon Dec 20, 2004 7:59 am
by billmac

Biogen's data does not show that Tysabri works better in isolation than in combination. The two studies cannot be directly compared in this way. It is very misleading to compare the percent change in relapse rate.

This seems to be a common misconception. THe two studies cannot be compared for a number of reasons, some statistical, but others involve the different baseline characteristics of the groups.

To make a long story short... the combination is probably better than either in isolation... but to test this directly a single study would have to directly compare a placebo1/placebo2 group, an avonex/placebo group, a placebo/Tysabri group, and an Avonex/Tysabri group.


Posted: Mon Dec 20, 2004 8:49 am
by HarryZ

Yes, comparing those two studies is not the best thing to do but unfortunately the two are often mentioned together in discussion. The fact that patients in the "combo" therapy trial had more disease progression to begin with clouds the issue and makes it quite difficult to come to much of conclusion.....especially when there hasn't been any other similar trials completed that I know of as yet.

There have been some neuros who have given their opinion as to using Avonex or other CRBs with Tysabri but I suppose we won't know more until additional trials are done. And that could take some time!


Posted: Tue Jan 04, 2005 10:30 am
by lottydotty
It seems to me that the real trial doesn't start until tysabri is out in the market and we the MS'rs as a whole give our feedback on the treatment. I mean really......... does it really matter which dr. says what? It all comes down to us and what we say.
My neuro treats the disease, not me as a person. Therefore I'm first in line to receive yet another drug. Do I feal lucky? No. Am I gonna do it? I don't know, but I have a month to decide. So guess what my mind will be consumed with for the next month. I don't think that's healthy in itself.
Why is it we are constantly faced with decisions? Like we don't have enough going on?
Right now it's tysabri. Then it will be something else that's new. And on and on.
I wish all well and desperatly hope tysabri is the answer for many. And for those it doesn't work for, never fear...........there's always something else coming that's new and improved.