FDA approves a label change..

[0485c10]

Reported in NY times 17 hours ago.

what is concerning is the label update does not include the jcv antibody test, which was the label update Biogen applied for. the article doesn't say that, but i watched when they made their request for a label update to add the jcv antibody test. and the fda didn't add that.

instead this label update has a table of pml risk...0.3 less than 2 years, 1.5 between 2-3 then drops to 0.9 after 3 years & identifies an added pml risk of people who used a immunosuppressioves in the past.

but the fda did not add the jcv antibody test--the article did say the test had been approved in Europe by the FDA

AND i did read, in another article, the the EU & FDA are planning to begin working together by distributing approval functions in drugs used in both places---this economy is dragging all budget down i think!

the jcv antibody test is scheduled to be available to the general tysabri population-none stratisify trial people- by october in the US so i hope this label change to identify the risk of pml is just a step toward that. the EU hasn't updated their label with the jcv antibody test either, just approved the test and allowed the test to be used. The EU adding it to the label will be another step for them, they just approved the test first. the fda has done neither yet.

http://online.wsj.com/article/BT-CO-...07-712561.html

[0485c10]

a link to the fda label...the label change--what has been added is on page 4. gotr licky when i found the lasbel on the fda site, i don't always find it, this time i did.

http://www.accessdata.fda.gov/drugsa...38s0475lbl.pdf

[shortcake23]

What exactly does this all mean? The label change? I'm still fairly new to all the lingo...

[MrsBones]

What exactly does this all mean? The label change? I'm still fairly new to all the lingo...

The information provided to patients and drs now reflects the fact that the longer you take Ty the higher your risk for PML and that prior use of immunosuppressants also increases the risk. Previously, only use of immunomodulators with Ty was listed as a factor.

The increasing risk (presented in the incidence per 1000 format) over time is now also included.

[0485c10]

immunssupresent is not the same as immunemodulators

I don't remember immunomodulators ever being listed as a risk factor, quite the oposite, it was never listed as a risk factor, for years, and this drug has only been around for a few, its been verbally stated that previous immunsuppressant use seemed to increase pml risk & then there was discussion of HOW long someon used an immunsupressant in the past like novatrone, cytokin, ect....
and then there was talk of how long ago the immunsuppressant was used..before it was just talk, now with this label change it's official & it doesn't seem to matter for how long or how long ago immunssupprestants were used... immunesuppresants should not to be confused with immune modulatos like betaseron, rebif & avvonex.

now any past use of an immunsuppressants are listed to cause an increase in pml risk OFFICIALLY.

we still have to wait and see how past use of gilenya affects the pml risk with tysabri....whether it will be like an immunemodulator or an immunesuoppressant?

but immunemodulators should not be confused with immunesuppresants. they are 2 different thing.

CONCURRENT use of an immunemodulator may affect the risk, that the fda has already disallowed & now with this label change they have said any previous use of an immmunesuppresant increases pml risk....but its been talked about for a long time, now its official.

the order a person has to use immunemodulator, tysabri then an immunesuppressant.,,,first tysabri , then an immunesupressant.

and a few people have skipped the immunemodulators & just started tysabri first in aggressive cases of MS

still the fda advises that tysabri is a 2nd line drug after one of the immunemodulators has failed.

[MrsBones]

I don't remember immunomodulators ever being listed as a risk factor, quite the oposite, it was never listed as a risk factor, for years, and this drug has only been around for a few, its been verbally stated that previous immunsuppressant use seemed to increase pml risk & then there was discussion of HOW long someon used an immunsupressant in the past like novatrone, cytokin, ect....
and then there was talk of how long ago the immunsuppressant was used..before it was just talk, now with this label change it's official & it doesn't seem to matter for how long or how long ago immunssupprestants were used... immunesuppresants should not to be confused with immune modulatos like betaseron, rebif & avvonex.

now any past use of an immunsuppressants are listed to cause an increase in pml risk OFFICIALLY.

we still have to wait and see how past use of gilenya affects the pml risk with tysabri....whether it will be like an immunemodulator or an immunesuoppressant?

but immunemodulators should not be confused with immunesuppresants. they are 2 different thing.

CONCURRENT use of an immunemodulator may affect the risk, that the fda has already disallowed & now with this label change they have said any previous use of an immmunesuppresant increases pml risk....but its been talked about for a long time, now its official.

the order a person has to use immunemodulator, tysabri then an immunesuppressant.,,,first tysabri , then an immunesupressant.

and a few people have skipped the immunemodulators & just started tysabri first in aggressive cases of MS

still the fda advises that tysabri is a 2nd line drug after one of the immunemodulators has failed.

Thanks for making my point again.

While there was nothing like ," Immunomodulators taken with Tysabri increases the risk of PML," there were indeed warnings that PML occurred in people during the trials and that those people had also been on another DMD (read immunomodulators) while taking Ty. Further, it explicity said that Tysabri should only be used as monotherapy. Pretty clear that the immunomodulators were considered a possile risk.

Having a immunosuppressant (steroids) be part of the TOUCH protocol questioning and requiring your dr's approval to take the next dose of Ty after steroids also is an indicator that immunosuppressants were also suspect.

The changes now are, as we both said, more explicit in the risk factors, such as length of usage, immunosuppressants,etc.

The previous verbage was vague on immunomodulators, but said enough to make it clear it was unwise to combine Ty with an immunmodulator. Previous immunosuppressant use, again, as we both said, wasn't mentioned and now is.

[0485c10]

you know it gets more complicated than that as i found when i read the fda transcripts on tysabri.

first the fda approved a new drug that was to be used with an existing drug, the existing drug had no serious side affects in over a decade of use--a "safe drug"

then it was combined with a new drug and this serious side affect with fatalities happened. tysabri was not originally designed to be a stand alone drug, it was designed to be a 'helper drug" to avenox when avonex had less than optimal results.

tysabri was originally designed to be a part of a due...

when pml unexpectedly happened the fda, said we have been premature we don't know if its the combination of a immunemodulator + this new drug or the new drug alone that is caused pml? we have to find that out first. when we know we might return ty to be used as a part of a combination or never again to be used even as a stand alone drug.

in 2006, the fda approved ty to be used as a monotherapy

so they re-approved tysabri as a monotherapy--if pml happened when ty alone was used, ty was the causing pml---not the combination. Perhaps then the combination could be returned again, for serious ms cases---or ty would be withdrawn entirely.

the risk of pml is low.

its been about 6 years since ty was returned as a monotherapy & tysabri alone has caused pml---so it wasn't the combination, it was tysabri that causes pml....

and with this label they are more clearly defining the known, proven risks that increase the chance of pml ...duration of use & past use of an immune suppressant.

immune modulatorshave never been indicated to increase pml risk--never it was ty that was causing pml--

but it is very tough to do a trial, double blind ect. to evaluate the conditions to to produce a sometimes fatal side affect. not a lot of volunteers for that trial...so we probably will never know if concurrent immunnodulator use increases the chance of pml with tysabri.

we have had more that 6 years of data of people who have used tysabri after a immunmodulator and after an immunsuppresant...

the the data has shown a link to past immunesuppresant use but not past immune modulator use...the statistics show past use of an immune suppresant increases risk, but no ties to a past use of immune-modulators.

actually immune-modulators in combination with ty has never been either proven or disproven as a risk factor----more its avoided in case it is.

that's something we will probably never know==unless you want to organize a double blind trial on it? past use of immune-modulators has not been statistically indicated after 6 years of data to increase the pml risk. immunesuppresent & duration of ty use has.

[lindaincolorado]

What am I missing ? I'm pretty sure I've read that after 3 years -from infusions 37-48 the risk drops down to .9 which is a bit less than 1/1000.
I've spoken to a couple people at Active Source saying I would like to know where the risk is at over 4 years.

[0485c10]

Good Point Linda--i just read it going up & down, i never noticed after 3 years it is below the pml risk on the label and what tysabri was approved for.

kind of like
0-2 years, below risk on label
2-3 years, above risk on label
3+ years below risk on label again
4+ uknown

i just read-0-2 much below risk on label
2-3 risk rises
3+ risk lowers
4+ risk unknown

[dontlika]

so, about the TOUCH program and immunosuppresants

"Having a immunosuppressant (steroids) be part of the TOUCH protocol questioning and requiring your dr's approval to take the next dose of Ty after steroids also is an indicator that immunosuppressants were also suspect."

So now what am I missing. My husband recieved his first dose of Tysabri and a 5 day course of IV solumedrol 1gram/24hrs. Any research on that?

I know he needed special permission from the Doctor to TOUCH to do this but it all went through very easily and with question. At his next appoinment he had the same issue as it had been 24 days since his prior steroid tx. Is this not something that has happened regularly?

Also, yes this is his first course of treatment and he was tested for the JC virus antibodies when the decision to use Ty was made. I was unaware that being tested before the prescribing was not normal protocol now? I knew it was new but thought it was protocol. Is he in a trial and we don't realize it??

He is JCV negative, but the Doctor said they would have treated him with Tysabri for 18 months had the test come back positive.

More confused the more I learn. Go figure.

jes

[0485c10]

I knew it was new but thought it was protocol. Is he in a trial and we don't realize it??

He is JCV negative, but the Doctor said they would have treated him with Tysabri for 18 months had the test come back positive.

More confused the more I learn. Go figure.

jes

yes he is in the stratisfy trial now, if he has already had the jcv antibody test--the test is still new. it should be out in the US market, for the general tysabri population sometime by october, if not sooner.

it recently was reported that all 102 people who got pml had the jcv antibodies- so there is virtually no chance of getting pml without having jcv antibodies---the test was only developed about two years ago, this is a new drug for all of us, if you would feel more comfortable go to an older drug & let your husband's ms get worse with the assurance that nothing new or uncertain is being used by your husband....that is an option your husband has too....

ivsm for the treatment of relapses is fine to do with tysabri, what has been advised to not do is pulse steroids, the routine use of steroids when relapse is not present....like doing steroids pre-scheduled once a month while using tysabri.

BUT i do know a person who is doing that for a particularily severe ms that is not responding to tysabri & hasn't responded to other meds, so her doc is ordering monthly pulse steroids, she tested negative for jcv antibodies and her doc is keeping a very close eye on her while she is doing it, with hopes that she will do this fopr a while then tysabri will kick in better and do it alone after, given time to be more effective--so it can be done for severe, unresponsive ms..luckily that's not your husbands case


http://www.bloomberg.com/news/2011-0...ease-risk.html

[dontlika]

Thanks for the answer

Thanks,
Guess we weren't actually told he was in a trial. This is some more good learning. Sounds like it is lucky though, as people prior did not have that test done in the past.

I understand that no one JCV negative has gotten PML but JCV does not cause PML, correct? It is just an indicator that you are more suseptible to the encepholopathy? How often do they plan on repeating the antibody test? I was told you could get JC virus anywhere at anytime??

Thanks about the ivsm info. That one threw me off.

On the upside, after 3 flares in 8 weeks and 3 rounds of ivsm, he has his 4th round of Tysabri next week and has had no side effects (tiredness or headaches) and no new overt symptoms! He never complains anyhow but looks like the epitomy of a healthy 33 yr old
thanks
jes

[0485c10]

I understand that no one JCV negative has gotten PML, but JCV does not cause PML, correct? It is just an indicator that you are more susceptible to the encepholopathy? How often do they plan on repeating the antibody test? I was told you could get JC virus anywhere at anytime??

hi jes, actually the jc virus does cause pml. most people have the jc virus, but a person's immune system contains it, so the person who has the jc virus can live with it harmlessly. i think there are some digestive virus like that too--we just live with them and they cause no problem. that is what the jc virus is like.

when a person is taking tysabri, tysabri prevents the immune system from getting into the brain. for people who have the jc virus it normally resides in one of the organs like the tonsils, bones, pancreas, or a few other organs. where the immune system is very successful at containing it, it does no harm.

the problem is when jcv gets into the blood stream it can travel & if it travels to the brain in a person who is taking tysabri, the immune system can't get into the brain to contain or fight it.....

once the jc virus gets into the brain it causes large lesions, the start of pml...its a bad situation because the pml that the jc virus started has to be stopped, but the only way to stop it, is to stop tysabri and let the immune system back into the brain to fight the pml. but the immune system when it fights the pml causes damage to surrounding brain tissue that can be very serious to called IRIS(?). you can look at some past post that discussed this.

the jc virus does cause pml. they needed to develop a blood test to identify if a person had encountered the jc virus and built anti bodies against it---because normally the jc virus can lie harmlessly dormant in so many possible organs, they needed to devolope a blood test to determine if a person was ever exposed to the jc virus, other wise without a blood test,there would be no way of determining where jcv was hiding?

we will need to have periodic retests of the jcv anti body test while using tysabri, once we test negative. because as you know already someone could be exposed to the jc virus anywhere and at any time?

when they release this test to market by October they should also make a recommendation on how often the jcv antibody test should be repeated when using tysabri. we are still waiting on that.

[dontlika]

04835c10 thanks

Hi,

Thanks again for answering my questions. I am trying to get a better grasp on it all and you are very helpful. I am fairly physiologically educated but far from knowledgeable.

Would it be correct to in some ways think of the jc virus somewhat like vericella (chicken pox)? Most people are exposed and have antibodies (at least in my day, I know vaccines are different now). It lay dormant until the immune system is stressed?

That said, if you are antibody negative for jcv then you have no titers and thus have not been exposed to it?

My husband had shingles at the age of 28. Is there any connection with unusual flares of a dormant virus, or would he have tested positive for varicella antibodies in order to have shingles?

Sorry about the direction of the question but I am trying to understand why he is antibody neg while in all likelyhood I have antibodies for jcv. Thank you for your explaination, but i guess i am unclear on one thing, if the virus (jcv) is dormant and hiding, would it still show up in the antibody test?

Also, thank you for explaining that JCV does cause PML. I was under the impression from the neuro that it just increased you chance of getting it, not realizing the general poulation that has the virus become active do not progress to PML as they are not on Tysabri??

Thank you, thank you....really trying here
jes

[0485c10]

i haven't finished reading your post

that chix pox shingles comparison was such a good one, i stopped to reply that it was so good, all i could think of some wierd digestive stuff, but the chix pox virus laying dormat then causing shingles nailed it--what the jcv is like!

i have a lot of time on my hands to read this stuff & i always want the dots to be connected before i stop trying to understand....mostly i get it right eventually and type what i have learned in l-o-n-g replies. most of the time its tmi, but i have to remember it in order of the connected dots.

at first they tried to test for the actual jc-virus in the blood & urine...that did not turn out to be reliabl;ew enough. i can find some articles on that attempt.

then they tried to test for antibodies to jc virus--whenever a body is exposed to a virus, the body makes antibodies against iyt & remembers it always..similar to if you already had the flu, you won't get that flu again.

same way with the jc viirus. but from wjhat i understand, a preson can get the jc virus and the symptoms might be sio mild the person does not know the have a "flu"..just some sore muscles and stuff. buyt even if it's only sore muscles, the body has produced anti bodies against it & thoose anti bodies can be tested in the blood forever.

i havn't had the jcv antibody test, but i am interesested to get it...i think evveryone can remember a time when that might have beemn it...for me when i was 13 i got a lot of repetitibve strep throats---was that the jc virus or did that cause my ms?

i'm excited about getting the blood test & i think too you could be exposed to the jc virus and give it to your husband, or he could go to the grocery store and get it while waiting in line at the cashier.

i think what your getting at is should you be tested too for the jcv virus because he could catch it from you?

mention it to his doc if you want, but i don't think its practical to test everyone who a person on ty encounters.

if you have the jc virus, its laying dormat in you and not active, so you didn't give it to your husband as his jcv antibody test showed & it will be more important that HE get periodic jcv ant ibdy test while he is on ty.

i gotta go someone at the door, i think thats what you are getting at?