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Just thought that this was something interesting to ponder. Co-administration of Avonex reduces Tysabri clearance by approximately 1/3rd. As you can see from the FDA label, Biogen/Elan did not think this would be a problem, but they did consider it... So not only may Avonex's immunomodulation combined with Tysabri's be too much, but Avonex's effect on Tysabri ALONE may boost T's immunosuppressive capabilities.

In other words, it's not just A+T we're looking at here, but rather A + T + 30%(T) or simply A + (1.3)T. This is obviously a very rough approximation, but it conveys the picture that there is more circulating T for longer when T is co-administered with A.

And, given what the A+T trials showed, this additional amount of circulating Tysabri over a longer period of time provides no apparent benefit!

I am just thinking out loud. This is for your comment...

From the FDA label:

"Drug Interactions

After multiple dosing, interferon beta-1a (AVONEX® 30 mcg IM once weekly) reduced TYSABRI® clearance by approximately 30%. The similarity of the TYSABRI®-associated adverse event profile between Study 1 (without co-administered AVONEX®) and Study 2 (with co-administered AVONEX®) indicates that this alteration in clearance does not necessitate reduction of the TYSABRI® dose to maintain safety (see ADVERSE REACTIONS, General).

Results of studies in multiple sclerosis patients taking TYSABRI® and concomitant interferon beta-1a (AVONEX® 30 mcg IM once weekly) or glatiramer acetate were inconclusive with regard to the need for dose adjustment of the beta-interferon or glatiramer acetate."

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

This is some interesting info on Avonex and reducing Tysabri clearance
from another MS board.

"Possible Explanation For Problems With Tysabri / Avonex Treatment


Yesterday, Morgan Stanley put out a research report summarizing discussions that they have had with PML experts. Overall, these experts seem to believe that the problems were causes by the combination therapy and not the monotherapy.

I have also done some research over the last few days and read what a number of other people have had to say in order to determine a possible explanation for the problems and whether the problems are a result Tysabri or the combination therapy. I believe the most likely conclusion is that the problem is with the combination therapy and that the monotherapy of both Tysabri and Avonex alone is perfectly safe. Below is my reasoning for concluding that the problem is likely with the dual therapy. I am not a scientist, so this is just a lay opinion, and should be taken as such.

I believe there are two possible problems with the combination therapy that could have led to the appearance of PLM in the Tysabri/Avonex treatment group.

1. PML is caused by the JC virus (JCV), which is present in about 85% of adults. In patients without immunosuppression, the JCV seems to remain and replicate in the kidneys, but is excreted through urination without causing any problems. In cases of severe immunosuppression, however, the JCV can get into the central nervous system (CNS) and cause PML.

It is believed that cytotoxic T lymphocytes (CTL) are needed to protect against the JCV getting into the CNS and causing PML. Th1 helper cells are apparently necessary in order to activate CTL.

Tysabri and Avonex (and all beta interferons) have a cumulative effect in reducing the number of Th1 helper cells. This is why it was theorized that there may be additive benefits from a dual therapy, due to this cumulative effect.

Avonex converts Th1 helper cells into Th2 helper cells. This changes the balance from one of a relatively even balance to one favoring Th2 helper cells. A balance favoring Th2 helper cells can also be seen in AIDS patients that develop PML. Given that there have been no cases of PML in patients using Avonex alone, this shift is apparently not extreme enough to cause PML by itself.

Tysabri blocks the migration of both Th1 and Th2 from the bloodstream into the CNS. Again, at least with the data that we have, it would appear as though this blocking of some of the Th1 from entering the CNS is not enough on its own to cause PML. Over 2500 individuals have used Tysabri alone in multiple studies and there has so far been no signs of PML.

So, basically, Tysabri blocks the Th1 and Th2 from entering the CNS, and then Avonex converts Th1 into Th2, creating a cumulative effect of reducing Th1, which is necessary for the prevention of PML. Either medication on its own does not have an extreme enough effect to create a problem, but the combination may in some extreme situation. (Even in severe AIDS patients, PLM is seen only 5% of the time, and so far in the Avonex/Tysabri group the incidence is about 0.4%, so there clearly are other necessary elements that are unknown.)

2. In the one year data, it was shown that Avonex prevents the clearance of Tysabri to a certain extent. Patients in the Avonex/Tysabri group had a clearance rate of Tysabri that was 30% less than the rate in the Tysabri only group. In other words, in the Tysabri monotherapy the drug clears from the body in about 30 days, which is why one must then get another treatment. In the Avonex/Tysabri group, however, only about 70% of the Tysabri cleared from the body after 30 days. This would seem to indicate that Tysabri built up in the body over time. For instance, after the second infusion, there would be 130% of the Tysabri in the body of the patient also taking Avonex as opposed to the patient on Tysabri monotherapy. After the third infusion, there would be 139% of the Tysabri in the body of the patient on Avonex also as opposed to the patient on monotherapy.

After many injections, this can add up to a large amount. While there did not appear to be any additional side effects due to this result, it is possible that the additional Tysabri in the body of the Avonex/Tysabri treated patients could lead to additional weakening of the immune system in addition to the one noted above.


These two considerations could explain why the dual therapy caused a problem that so far has not been seen in the monotherapy. While I am not sure that there is any reason to believe that the buildup of Tysabri would weaken the immune system further, it would explain why the incidents of PML did not appear until after over two years of treatment.

This same buildup, however, does not occur in patients treated with the monotherapy, so there is no reason to believe that any addition side effects, including PML, would develop over time. In essence, the effect that Tysabri has after 5 days is the same as it would have after 500 days since it clears the system and then is just replenished with the next infusion. It would be similar to drinking one glass of wine every day for 30 days. You are in no danger of getting drunk, because the previous alcohol has cleared your body before you drink the next glass. And, the 29th glass on the 29th day would have no more effect on you than the 1st glass on the 1st day. Similarly, Tysabri would have the same effect on the immune system after the 1st infusion as it would have after the 29th infusion."
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That's pretty strong "certainty" there. How do we know that? Who is making that statement? If there is definitely numerous research studies and substantive medical evidence and supporting information for that specific "guarantee", then GREAT! Did the FDA allow that specific type of statement be made?

I just can't find it, is all.

There is a post on another forum by an attorney, that I thought was pretty good in response to that exact same post that you just did, better.

I hope she doesn't mind, but I'm going to borrow her words, because she says it all pretty well (but then you know lawyers, they do have a way with words):



EDIT: By the way, better2together, you're not the same person who posted it over there, also, are you? That person is an Elan "investor". Oh, yeah.........and who also posts over on the Yahoo/Elan message board. Who was it who earlier said something about the dependability or reliability of company investor's words from the Yahoo board?

Ok........here it is:



All I'm saying is we ALL always have to consider the "sources" of anything and anyone. Including myself, of course!

I, for one, do highly respect Arron's opinions on things.

Deb

SECOND EDIT: Oh, and now I'm cracking up! And if you are the same person, then those other posts that I posted and identified in another thread here as being from another message board (regarding what other drugs those patients taking Tysabri had been on) was ALSO posted by that very same "investor"! So, those posts by that investor did more harm than good to the companies, in my opinion!

And in case anybody is just "wondering", I am not an investor in anything.......except for my own health and welfare, of course, along with other people's health and welfare.

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Deb,

I'm not not the same person who posted it over there.
But I try to provide this board with information that I hope is useful for everybody.

Regards,

Better2gether
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Ok, thanks for answering, better.

And yes, I am in favor of hearing from many sides and perspectives.

Thanks again for all the info you post.

Take care.

Deb

Hi Deb, just to be clear, I posted the quoted comment in response to a specific post where someone was potentially pretending to be a Biogen employee.

In the 99.9% of junk on those finance message boards are a few nuggets. We welcome that .01% with open arms.

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.