This Is MS Multiple Sclerosis Community: Knowledge & Support

We had my wife's first visit with her Neuro since Sept of last year, at which time she discontinued her Tysabri infusions due to being at the 2 year mark. 3 months after her last infusion she had about 5 days where there was a tingling/electric shock type feeling in the upper rear right portion of her skull (like when your foot/hand falls asleep). About 4 weeks ago she started having episodes of dizzyness accompanied by slurred speech which is still going on, happens between 8-12 times a day for 5-20 seconds at a time.

Well the Neuro today ordered a steroid pulse and informed us that between 4-6 months out from discontinuing Tysabri that there is a risk of IRIS or Immune Reconstitution Inflammatory Syndrome (and that it is important to get on another MS drug once the Tysabri has cleaned out of the system). This wasn't mentioned in relation to PML, but to anyone stopping Tysabri after being on it for a long period of time.

So, not only is there PML to consider with Tysabri, but also IRIS once a patient comes off Tysabri which seems inevitable at some point considering the unknowns around long-term Tysabri use.

I have always thaught that IRIS has been connected with PLEX (plasma exchange), only...

See:
1) FDA warning (February 2010): http://www.fda.gov/Safety/MedWatch/Safe ... 199965.htm

2) Professor David Bates article (US Neurology):
"During recovery from PML, immune reconstitution recovery syndrome
(IRIS) is an expected condition. This appears universal in PML
associated with natalizumab, unlike PML in AIDS, regardless of whether
natalizumab is removed rapidly or simply discontinued. IRIS generally
occurred four weeks after stopping natalizumab treatment, but in some
cases it occurred earlier. Corticosteroids, sometimes multiple courses,
given early in the course of IRIS appeared to lead to improvement in
most patients. To date, most of the natalizumab-treated patients who
developed PML have survived, but exhibit varying levels of disability."

3) The Lancet Neurology (April 2010): Clifford DB, DeLuca A, Simpson DM, Arendt G, Giovannoni G, Nath A. (Department of Neurology, Washington University in St Louis, Saint Louis)
"Management of PML has routinely used plasma exchange (PLEX)... Exacerbation of symptoms and enlargement of lesions on MRI have occurred within a few days to a few weeks after PLEX, indicative of immune reconstitution inflammatory syndrome (IRIS). This syndrome seems to be more common and more severe in patients with natalizumab-associated PML than it is in patients with HIV-associated PML."

Hi Johnnymac.
What you write may be symptoms of PML.
So I want to ask you if your wife was examinated about PML when first symptoms appeared.
If so what they do? MRI and spinal fluid? They look for virus DNA in liquor cerebrospinalis one or two times? If two, in two different labs?
I never heared or read that IRIS comes without PML.
Thanks for answers.

Writing you husband of PML case no. 5 from germany.
Best wishes to you and specially to your wife.
Pit

Our Dr did not mention any concern of PML, Courtney had her last infusion just over 6 months ago and the dizzy spells/slurred speech didn't start until 4 weeks ago. I'm pretty comfortable our Neuro would be pretty careful about this, and we're definitely on the the lookout for any new symptoms. The neuro definitely said that because Courtney didn't get on another MS treatment after the 3 month tysabri vacation period, that she was at risk of IRIS and that it could have caused her exacerbation, and that she definitely believed Courtney was having an attack. First steroid infusion was last night, the dizzy spells seems to be much fewer and not as sever and only a couple of instances of slurred speech last night. This morning she mentioned having a little better balance as well, 2 more days of the roids and hopefully the new symptoms will be gone. We have a checkup in 2 months with the Neuro, if Courtney has any additional symptoms we'll definitely call the neuro right away.

JohnnyMac:

This is the February 2010 update to the Tysabri prescribing information


Additional Information for Healthcare Professionals

* An update to the Warnings and Precautions section of the drug label has been added to inform healthcare professionals that the risk of PML increases with the number of Tysabri infusions received
o There have been no reports of PML in patients treated for less than 12 months since Tysabri's remarketing.In patients treated with 24 to 36 infusions, the overall worldwide rate and the rate in the U.S. of developing PML is similar to the rate seen during clinical trials (1 case per 1,000 patients treated). Outside of the U.S., the rate is approximately 2 cases per 1,000 patients.The reasons for this difference are unknown. There is limited clinical experience beyond 36 Tysabri infusions either in clinical trials or in the postmarketing setting.
o PML is diagnosed on the basis of clinical symptoms, MRI findings, and the detection of JC virus in the cerebrospinal fluid.
o Tysabri should be withheld at the first sign or symptom suggestive of PML.
o Continued clinical vigilance and close monitoring for the signs and symptoms of PML as dictated by the TOUCH™ Prescribing Program is necessary.
* An update to the Warnings and Precautions section of the drug label has been added to inform healthcare professionals about the occurrence of Immune Reconstitution Inflammatory Syndrome (IRIS) in patients who developed PML and subsequently discontinued Tysabri.
o IRIS is a rare condition characterized by a severe inflammatory response that can occur during or following immune system recovery, causing an unexpected decline in a patient's condition after return of immune function.
o IRIS has been reported in patients who discontinue Tysabri as a result of developing PML, but not in patients who discontinue Tysabri for other reasons.
o Many patients who stopped Tysabri due to PML and who received either plasma exchange or immunoadsorption (measures taken to decrease circulating Tysabri levels) developed IRIS days to several weeks after these treatments.
o Healthcare professionals should monitor their patients for the development of IRIS and appropriate treatment of the associated inflammation after stopping Tysabri should be undertaken.


Its pretty clear that IRIS (at least logically) doesn't occur unless a patient has been treated for PML.

My reading of this is that your neuro unfortunately skimmed the update and only focussed on the last bullet point, thereby concluding that all patients who have discontinued Tysabri are at risk of developing IRIS.

Sorry man. You might want to let your neuro know that she's wrong...

If you look at the wording carefully, the first bullet I quoted absolutely leaves room for interpretation, with IRIS mentioned in the absence of PML. Tysabri modifies the immune system, and when stopping the treatments there very well could be a period of immune reconstitution.

The second bullet says it hasn't been "reported" in patients who discontinue Tysabri for other reasons. Is that because Dr's have just been calling it the "rebound" effect or just a MS exacerbation. IRIS info is pretty new still.

The last bullet is very open as well, not saying monitor patients who develop PML for IRIS, but just to monitor increased inflammation after stopping tysabri.

These Pharma companies are worried more about their stock prices than the people taking their drugs, and their carefully worded warning and statements are a testament to that. Just be careful, that's all I'm saying.

At work right now - so let me be more direct: There's lots of things that MS'ers take that can modify the immune system (some much more powerful than Tysabri - see Campath) - none of them have been found to cause IRIS. In MS patients, IRIS appears to be direct by-product of the processes that are used to get Tysabri out of a patient's system as quickly as possible following a diagnosis of PML.

I did an exhaustive search, looking for links between IRIS and Tysabri use, without the a PML linkage. The only thing that comes up is another warning posting of yours on a different MS bulletin board.

Most people who take Tysabri realize that it is a leading edge medication that has potential unknowns linked to it. Newbies browsing these forums don't need to be scared away from a very effective treatment with a posting that is at best hearsay, and at worst drug-company-conspiracy-inspired garbage.

Your postings on this subject are not benefitting anybody, and could in fact be causing a real dis-service to somebody weighing the REAL pros and cons about starting this therapy.

Call your neuro, and ask her why she is the only neuro in North America spouting this crap. She will backtrack.

Why does information that shows Tysabri as being a possible danger considered to scare away newbies.? Should they not read all the information available about this drug so they can make an informed decision about whether they want to use the drug or not?

Sure Biogen's competitors will take every opportunity to cast a shadow on Tysabri. This is no different in how Biogen operates. These drug companies take pot shots at each other all the time in the hope of gaining an extra per cent or two of the MS drug market. That translates into millions and millions of additional dollars if they are successful.

Dont' you remember when Biogen told us that Tysabri was safe. Then after the first cases of PML, they said it was taking the drug in combination with other immune suppressant drugs that caused the PML. Then when monotherapy patients ended up with PML, Biogen told us the risk was only 1 /1000. Then more patients started getting PML and the risk outside the US is around 1/500. So please don't tell us that other posters are spewing garbage when they point other possible dangers with extended use of Tysabri.

Yes, Tysabri has more efficacy than the CRAB drugs but those drugs have an abysmal record of efficacy when it comes to MS.



Perhaps they aren't benefiting your opinion of the drug and you don't agree with what is being said. That is your perrogative but please don't jump all over someone because they happen to have a different opinion



Please don't insult us with this kind of comment. There are a lot of neuros around who don't think much of Tysabri just as there are others who think it is OK.

Harry

HarryZ, -though I am aware of your overwhelmingly negative view of Biogen, and have over the years witnessed many of your back-and-forths regarding Tysabri ( the highlight would have to be your success in temporarily driving Bromley insane a few years ago) - I will try one more time to explain my issue with the original post:

The 'opinion' that has been put forward, is that the withdrawal of Tysabri alone can cause IRIS. As someone who was on Tysabri for 27 infusions, and has now been off for 5 months, you can imagine that the first posting in this chain would cause me (and others of my ilk) some alarm.

The problem is that the 'opinion' is being put forward as fact, based on a professional's statements, and then tied erroneously, and out-of-context to the Tysabri prescribing information update.

ps. Your compatriot-in-suspicion of all things Biogen (RuSmolikova), had no problem refuting Johnny Mac's statements. I note in your extensive posting, that you don't specifically address the issue - can withdrawal of Tysabri alone cause IRIS? Perhaps you have something to add to the discussion about this?

Let's just say that my less than dim view of Biogen was well earned by them over the many years I have followed their introduction of MS drugs. As for Ian....unfortunately you have only read one side of the correspondence between the two of us. Ian has written me a number of private e-mails which if you saw would likely change your entire opinion of what transpired.



Interestingly, I didn't quite get the same take as you did but that's what happens when different people read the same information. I have no qualms about you expressing different opinions and pointing them out. It's the way you "trashed" the opinion of the other poster.



Then say that. There wasn't any need for you to make the other comments that you did and that's what I object to.



Disagreeing, refuting, not liking the comments of others is all part of internet forum discussions. It goes on all the time and has on this forum as well. It's when you make personal comments towards others that isn't needed, required or allowed on ThisIsMS. And that's my sole point.

As for Tysabri and IRIS....I find the comments interesting from all sides. There certainly isn't a lot knowledge about it as well...almost as much of the unknown as there is about the long term safety of Tysabri!

If and when I decide to make a personal opinion about IRIS and Tysabri, I'll will do so. Until then, I just don't like to see personal unpleasant comments made towards others when someone doesn't agree as to what a person has stated. There is no place for that here.

Take care.

Harry

Point taken.

Johnny Mac - It was not my intention to be insulting, just convincing. If I offended you, I apologize.

All I was doing here is posting our experience, and when confronted saying my Neuro is "wrong" by posting the latest Tysabri FDA release I stated my opinion on those bullet points, I didn't bring them up.

I'm not trying to turn anyone away from Tysabri, there are no good options for MS patients, its a decision of the lesser evil for each individual. All I say is talk to your neuros and ask them about it. Our MS Clinic has been on the forefront of Tysabri since before it was released and was one of the clinics running Tysabri clinical studies, so I'm not concerned about my Neuro being wrong on this, I trust she knows what she is doing.

Do I dislike Pharma companies, absolutely, but at the same time they make my wife's life more manageable which I'm thankful for.

no offense taken, this is an important topic and definitely worthy of discussion.

This article was just brought to my attention by a friend, looks like our Dr knew what she was talking about

http://www.medpagetoday.com/MeetingCoverage/AAN/19507

Just to make sure I fully understand this...... I have now stopped Tysabri....
Is it not just that I do not have the protection Tysabri offers, but that I can get worse, because I stopped it? That stopping the drug can actually make me very poorly? That it can cause me to have many attacs in a relativley short time span?

I was never informed about this!
My last infusion in mid march made me bedbound, I could hardly walk to my car parked just outside the main entrance. The day before I did 1 hours of watter arobics with my physical therapy group. I'm still in bed most of the day, and feeling lousy, dizzy, weak, headaches. It all comes and goes.

My neuros have not doen anything about it, they have not mentioned possible pml, they have not mentioned anything about IRIS, they have said its probably just another ms attack. Now they are stuck in Canada at the conference and cant get flights back. I'm waiting to test for antibodies, whatever that means...

Sorry about the moan, but I got a bit conserned about this IRIS thing....

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<div>I have lived with ms for 8 years. The last year has been hell, I've gone from shite to even worse every single month, until my liberation in May. </div>