Evolution of the Risk of PML from Tysabri

[Quixotic1]

Hi, guys.  I wanted to talk briefly about what is being found out about the risk of PML.  First I have to state that the current recommendations are still in effect.  The Risk of PML is greatest in the setting of a positive J-lymphocytesC virus,  greater than 24 months of Tysabri, and concurrent use of other DMD's or steroids.  Those are old recommendations, and new info will change them in the (near?) future.

PML is caused by the J-C Virus.  A little more than half of all people have been infected with the JC virus.  It generally lives asymptomatically in the brain unless something has occurred to cause the immunity of the brain to be compromised.  Tysabri prevents T-lymphocytes from entering the brain across the blood-brain barrier.  In a nutshell, T-lymphocytes are instrumental in helping the body defend against infections in the body - especially viruses.  

So people who are NOT infected by JC have essentially NO susceptibility to PML.  The equivocation comes from the occasional false negative of the JC blood test, so that the very rare person with PML and a negative result on the JC virus mostly likely actually has the virus which was not detected.  There was some thinking that a Tysabri vacation could help prevent PML.  I have not seen this evidence.

Now - what I am about to talk about is not published and no one should act on it, but it is very interesting.  My neuro is a Tysabri researcher and he has been working with a lab here studying a new blood test for the presence of the JC virus and what the new results mean for the risk of getting PML.  The test that up to recently has reported that the virus IS in the body or NOT in the body.  There is a new assay that can report it's actual titer.

The research from multiple centers is showing that some people with the virus and a negative earlier test actually DO have the virus.  I am one of these.  I was always negative up until last fall.  My doc told me that statistically people with a titer below a certain level have NO increased risk of PML.  Above that level the risk of PML goes way up, possibly even higher than the 1 in 1000 which is the standard risk quoted.  

Interesting enough, it is not a linear risk, meaning that your risk does not seem to go up as your titer goes up from zero.  These are the numbers that my neuro gave me, but I don't know the exact units.  He says that the real risk of PML comes with a titer over "0.91".  Below that level the risk is essentially non-existent.  It doesn't matter if the titer is 0.2 (my level) or 0.85.  Those both have the same risk.  Above 0.91 the risk appears and would be reason to stop the Tysabri immediately.  

I didn't discuss how the use of other DMDs affects this, but my neuro says that length of use does not affect the risk - as long as the titer remains below the 0.91  point.

I find all of this very interesting.  It means that the insecurities surrounding Tysabri's use are likely to be resolved soon and we won't have to deal with "vacations" and such.  This is good, because the reports of people who stop Tysabri show that many have a significant relapse within 4 months of stopping the drug.  Next month I have my third anniversary.  I feel good on it and much less fatigued.  I don't want to stop it.

On to another topic.  I have pretty much lost all my veins - not because of the Tysabri - but because I am such a hard poke that the veins are destroyed in the process of trying to find them.  Instead of getting me on the first try, now it is taking 4-5 tries. This includes blood draws.  The nurses are encouraging me to consider getting a "port".  I am beginning to get very tired of having a dozen healing bruises on my hands and arms all the time, but a port seems like an awfully big thing to do for "just" an IV or a blood draw, but I DO NOT want to stop Tysabri if I don't have to.

Has anyone  ever had a port for vein access?  

There is more news about Tysabri I'll add later.

Quix

[PeninaD]

John Cunningham Virus is quite prevalent, and normally is not more annoying than a typical cold.  It's when it is able to cross the blood brain barrier that things get way too interesting.

[kwarendorf]

Quix - I have wondered how someone without JCV acquired it. Is it airborne etc.

Before starting Tysabri I tested JCV -. After 20 infusions I tested JCV +. Now I wonder if I had it earlier, at undetectable levels. It's a moot point for me, as at the same time it was determined that Tysabri was no longer working for me (fetuin-A CSF level).

No point in risking PML if the Tysabri isn't working :-) I've moved on to rituximab.

Kyle

[immisceo]

Interesting stuff! Thanks for bringing it to our attention. Penina as well.

It's great to know that specific research is ongoing and starting to yield some clarity on this issue. Tysabri is just too important an option for so many of us. Delighted to hear such a giant question mark surrounding its use is getting a smaller.

[PeninaD]

Had you seen this from last week's AAN 66th Annual Meeting?
http://www.medscape.com/viewarticle/824614

"PHILADELPHIA, Pennsylvania — A new study shows that combining 2 markers for risk for progressive multifocal leukoencephalopathy (PML) during long-term therapy for relapsing-remitting multiple sclerosis (RRMS) with natalizumab (Tysabri, Biogen Idec) may expand the population of patients at risk compared with using the traditional single parameter of positivity for JC virus (JCV) antibody alone.

"Patients that had high antibody titers had lower expression of CD62L. And actually this was only true for patients that had not been immune suppressed beforehand," Johanna Breuer, MSc, from the Department of Neurology at the University of Münster, Germany, told Medscape Medical News. Previous studies showed that JCV antibodies could be used as a predictive marker for PML only in patients who had not been immunosuppressed.

Currently, patients are stratified for PML risk according to previous immune suppression, the duration of natalizumab treatment, and the presence of serum anti-JCV antibodies at a certain level."

[karryon55]

Hi Quix,

I have had a "Power Port" for over 2 years now & I often completely forget I've got one. My port is placed in my upper breast/chest area so I can wear most tops without anyone seeing the scars. I was told last week whilst getting mine flushed that they are now placing them in people's arms but some are not happy with this as they can feel them when moving their arms.

My veins were so bad that I was having PICC & Central lines for the 3 years prior to my port going in. Unfortunately after spending over 4 hours trying to get the last PICC line in I was told that I could not have it removed because they needed to use this existing line to thread the port. I also got a couple of pulmonary embolisms because they were trying to break up some old clots from previous PICC's that had been removed repeatedly.

I have had a really great experience with my port & it has taken away the worry of not having any access if I were Neutropenic again. I was at a stage where central lines were often used & this was high risk for a septic Neutropenic. I can have a 3 tesla MRI with no problems. At first they were worried it would heat up so they would pull me out for a while between scanning but now as this isn't happening I just have them straight through. When it comes to MRI's they will count any other metal you have so if you do have more metal anywhere then having a port implanted "may" compromise MRI's.

I have two incisions which is needed for the implant. The port is usually placed behind a bit of fatty tissue. I use a numbing cream most times but have had it accessed many times without. It's important to put the numbing cream on at least an hour prior & cover it with a clear non stick dressing, just don't rub the numbing cream in. I have Rituximab infusions which are 6 monthly so I do go in to get it flushed every 6 to 8 weeks when it's not in use.

If you have any questions whatsoever please ask away. :-)

Take Care,

Karry.