This Is MS Multiple Sclerosis Community: Knowledge & Support

I've been reading some other message boards, and there is much discussion regarding all of the other medications that Tysabri clinical trial patients were taking along with Tysabri.

I have ONE question. Why in the world would you run a clinical trial on a medication that you aren't even sure how it works, how well it works, etc. by itself ALONE, and allow so many other drugs to be taken along with it? Especially with something as strong as Tysabri??

How can ANY data from ANY clinical trial on any new medication be relied upon that way? Good or bad. There would be absolutely NO way to determine which drug or which particular combination of drugs caused the improvement or deterioration!

Uh...........is it only me that doesn't see any common sense in conducting any clinical trial this way? If a patient in a clinical trial needs additional medication, they should receive it immediately, but then they need to be removed from the trial.

Now I have no idea if the below is accurate or correct for sure, because I'm taking this from another forum, but look at this! Why were these patients ever in the clinical trial in the first place? You mean they met the criteria having all this in addition to MS? I have to admit, this bothers me a bit.

Here are some excerpts from another forum. Again, I have no way to confirm the accuracy.





Well, all the more reason that if desipramine is EVER put into clinical trial, why I want to stay "involved". No WAY should most of that be combined with a tri-cyclic. Not only for keeping the clinical trial data "clean", but for the complete safety of the patient. And me staying involved would assure that nobody could allow such "skewing" of the data to take place, because I'd scream to the high heavens about it. And the patients would have to meet a strict diagnostic criteria of having MS. And that their associated medical and physical symptoms were due to the MS itself, not additional "serious" diseases.

Man!



Deb

EDIT: Besides, common sense also tells you that (like in that one patient), you don't combine an immunosuppressant type drug such as all those allergies medications along with a VLA-4 antagonist!!! WHO was that patient's head study doctor???? Pharmacology/toxicology is NOT rocket science! And Levitra, for example, is a PDE inhibitor! Oh, for crying out loud!

Zantac...........oh, man. That interacts with lots of meds!

SECOND EDIT: And wait a minute! These patients were also taking BOTH Avonex and Tysabri. That just dawned on me! I'm sorry, good neuros should know better than this (i.e. just keeping on prescribing med after med! What's up with THAT?)

Just for an example. Let's start with a PDE inhibitor. Pretend we're a common sense neuro.

Number one: We have a patient on a PDE inhibitor. We know that a PDE inhibitor in and of itself has anti-inflammatory properties. In ADDITION, we also KNOW from many studies, that a PDE inhibitor has MOAs on integrins (VCAM1 and VLA-4). Common sense IMMEDIATELY tells you to "stop" and look this up further if you are either putting this person on an integrin medication (Tysabri) OR an interferon, either one. (Or even if you have someone on Tysabri or Avonex, before adding something like a PDE inhibitor. So which came first is irrelevant for this exercise.)

Ok........let's look it up. Here is just ONE fairly clear "heads up" for us:



Ok.........BINGO! Nope, better not do it (i.e. prescribe a PDE inhibitor to this patient OR take the chance of allowing all these medications to be taken together). Too much is unknown about how these two drugs, (Avonex and Tysabri) alone will interact, not to mention the fact that we already aren't sure how Avonex and Tysabri act by themselves singley. Better not throw in or allow a THIRD known interactive drug into the mix! Not to mention, let's just play it on the safe side for the patient. (Is THAT a novel thought? Excuse my sarcasm, but I couldn't help myself.)

And how long did it take me to look this up??? Five minutes at most?

Ok..........here I go, huh?

Ok.........just what WAS the criteria to meet for the Tysabri/Avonex trial?



Ok......No comment. All I can say is how interesting!

Oh, I guess I'd have to also say "that's it?"

Hey, I've seen people be diagnosed and un-diagnosed with RRMS constantly! What are the determining factors that are to be used in order to adequately determine that clinical trial participants have RRMS in the first place in order to be eligible for this trial? Based on what or which particular test results or diagnostic criteria? Poser, McDonald, Schumacher's? LP, MRI only, diagnosis by exclusion, the doctor's "gut feeling", all of the above?

Remember, I myself was told I was the "perfect" person to be in the clinical trial I started (which was NOT the Tysabri trial), when even my neuro himself questioned that I was due to my unpredictable, shall we say, test results. He called the pharma company and he said the company told him I was the "perfect" candidate for the trial. (Remember, MRIs clear, LP clear, no way to determine for certain about whether or not I have had "two separate exacerbations" which led my neuro to wonder if I didn't have either benign MS or slowly progressive MS, etc. My diagnosis was purely a diagnosis by exclusion at the time.)

Deb

OddDuck,



Boggles the mind, doesn't it?!! A friend of mine who has done a fair amount of MS research made the same comment to me months ago. Taking these other drugs at the same time can possibly have all kinds of effects on the trial data yet the people conducting the trials continue to allow this!!

Harry

Ok a bit of info that may help understand a bit more...

The drugs mentioned are small molecules ie, synthetically made to agonise or antagonise a specific receptor! They are non-natural molecules that the body will try to get rid of them.. they are recognised as foreign particles.

Toxicity of these molecules generally arises from something other than the drug hitting the target. perhaps it is a chemical group added to the molecule in order to increase its solubility, or a blocking group that prevents its metabolism so the drug stays in the body longer...

The clinical interactions seen with these types of drugs tend to rely on drug metabolism issues (other interactions do occur though eg 2 x sleeping tablets = dangerously sleepy). The cytochrome P450 enzymes are responsible for breaking down these drugs so they can be removed from the body. Interactions occur when two drugs administered are removed by the same p450 enzyme, they both compete for the enzyme, one wins and is removed from the body whereas the other stays in the body uncleared, patient takes more drug and an accumulation occurs leading to possible toxicity due to increased blood concentrations.

Ok so heres the more difficult part... big pharma companies are getting very poor results with these synthetic molecules and are moving more into the biologicals market. If you administer a biological drug, the body recognises it as self and makes very little effort to eliminate the drug, hence it stays in the body a lot longer to have some form of action, the resulting toxicity of these molecules are a result of their mechanism of action rather than modifications made to molecules in synthetic drugs. (eg if it is meant to damp down the immune system, how do you contol it? How do you stop it destroying the immune system?)

In an ideal world there should be very little interaction between a biological drug and a synthetic drug.. unless they work on the same target and the interaction is a pharmacological one. If you administer two biologicals which dont act on the same target there should be little inteaction.

oops got a meeting to go to will continue this later ...

I agree. That's the example I gave and why I gave it.

Tysabri and a PDE inhibitor both act on VCAM1 and VLA-4.

And that's the reason why I figured desipramine and levetiracetam would probably be ok together. They do not act on the same targets.

So, in any event. We totally agree, and some physicians are apparently (and excuse the phrase) stupid or negligent, or both.

In any event, it appears they are finding that their "complicated" philosophies about what "should" or "shouldn't" interact are not proving to be reliable. Let's just keep it simple then, and safer.

Deb