New Clues to link between Tysabri and PML

[ru4cats]

This was posted on another MS forum, and I found it interesting. You can google WebMD Tysabri and pull it up, or here is the URL.

http://www.webmd.com/multiple-sclero...-brain-disease

[Kimba22]

Perhaps most concerning, 10 study participants had evidence of the JC virus in their blood but tested negative for antibodies to it. That suggests current tests for the virus may be missing some patients who could be at high risk for PML

Additionally, Birnbaum said it was "disquieting" that researchers found evidence of the JC virus in patients who then tested negative for antibodies to it.

"Thus, testing individuals for exposure to JC virus by measuring antibodies to the virus may be insufficient to fully assess their risks for developing PML," he said.

Disconcerting to realize that none of us on Tysabri are exempt from the risks of PML, even with a JC- status.

[ru4cats]

I had the same thought Kimba, but at my age (62) I've decided it's a risk I'm willing to take. So far there isn't anything out there as effective as Ty, other than perhaps SCT, and that's a procedure I'm NOT willing to try.

[KatieAgain]

I knew JCV- people can still get the virus.

What stood out to me was the researcher stating 1 in 75 people are getting PML after two years on the drug. Did I read that right? I don't think that is what they have been publishing is it?

Any insight on that?

[Kimba22]

It's also been my understanding testing negative did not take away our risk for PML, since any of us can be exposed to the virus at any time. This sheds more light on the fact that a more sensitive test is needed to pick up the JC antibodies in everyone.

Right now, the risk of PML in patients treated with [Tysabri] for more than two years is about one in 75 patients. That's a very high risk," said study author Eugene Major, a senior investigator at the U.S. National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md.

That number is a whole lot higher than I ever read, too. Stats like that make it sound extremely risky for anyone on the drug more than 2 years.

[Marco]

The article also suggests "30 percent to 50 percent of patients with PML die within a few months of diagnosis.
The Tysabri-related PML deaths are UNDER 25% according to every statistic I have ever seen. Someone's numbers or definitions are wrong. Maybe HIV or organ recipients have a higher PML death rate, but the numbers certainly are not consistent. It certainly makes you wonder whose numbers you should trust.

A few years ago, I think both doctors and patients had more fear about Tysabri. Due to the outstanding efficacy numbers I think more people are willing to take a risk. Today, I think patients are staying on Tysabri longer than ever. I think doctors are more willing to put "higher risk" patients on Tysabri. I think the JCV titer test has people feeling more confidant about taking Tysabri if you are JCV+. I keep seeing terms like "JCV low titer" and personally believe that is a mistake. Then again, people don't generally look at 1 in 10,000 and believe they could be that 1 (unless playing the lottery).

[KatieAgain]

1 in 75...that is not good. That isn't playing the lottery...that is pointing your finger at people and playing Eeinie, meanie, mieni, mo! Oops...your it! So very sorry.

The article actually came from a reputable institution, but I do wonder about the research parameters.

I contacted Biogen today about the article. Discussed this with them for close to an hour. They are reviewing and I believe a statement will be coming in the near future. Transparency is important for all concerned.

[Marco]

Katie,
It's a reputable institution, but the numbers do not add up or the reporter failed on many levels. I am not making light of the risk of PML, but rather saying we need to take the numbers (as posed) with a grain of salt.

If you take 440 PML patients (from the article) with a 30-50% death rate (from the article) that would be 132 to 220 deaths. Unless Biogen is hiding a few to several dozen bodies somewhere the numbers (as cited) do not coincide with the information Biogen has released.

Again, PML should never be taken lightly, but I question the numbers; because they appear to be wrong.

[KatieAgain]

I absolutely agree Marco. That is why I called Biogen.

This article was posted on Web MD! Oh geez... I personally think it was irresponsible of the institution and Web MD to publish this info. This is directly contradictory to what Biogen, our MS Specialists, the Touch Program have been telling us. This information is either so blatantly wrong, someone is not telling the truth, or a new discovery has been made. Which in any of those cases, one would think that the FDA would have been notified immediately and issued a statement.

Someone did not do their job. And someone needs to be held accountable. I think it's going to happen, because I started the ball rolling. In fact, Biogen has scheduled a call-back to discuss next week.

You are right when we are talking about Tysabri and PML, we can't be too careful. Had the sources been different, I would have blown it off as bad info. I personally think it is bad info...really bad info...but as an informed Tysabri user I want transparency and accountability.

It is my responsibility to be educated. It is Biogen's responsibility to provide me with the correct information to make informed choices.

If anyone sees any more articles on this, I sure would appreciate them posting it here in this forum.

BTW...I am getting TY Infusion number 7 tomorrow, because right now...I am solidly backing Biogen, and TY has literally saved my life and is keeping me stable until such a time when I can start Tecfidera.

Thanks to RU4Cats for starting this thread. Transparency...my new favorite word.

[onlyairfare]

The original article referred to seems to have been published online in JAMA Neurology on March 24. It refers to enrolling 49 MS patients and 18 healthy volunteers. Then blood samples were taken at regular intervals from 23 MS patients (what happened to the other 26?). At that point they lost me.

Something funny is going on with the numbers. And the 440, where did that come from? The JAMA study was done at UT Southwestern, how did NINDS get in there?

Anyway, I agree, confused or bad reporting. I'll wait for more information and a better explanation. Of course I do not take Tysabri so that is easy for me to say.

I am JCV positive and my doctor told me that the roughly 1 in 100 chance does not apply until, as a high-titer JCV patient, I have taken Tysabri for more than 2 years. Nowhere near 1 in 75 of all comers.

[dyin_myelin]

Thank you Katie for your due diligence! The fact you were able to hang in on the phone discussing statistics is an ad for Biogen in and of itself.

[Marco]

Something funny is going on with the numbers. And the 440, where did that come from?

I am JCV positive and my doctor told me that the roughly 1 in 100 chance does not apply until, as a high-titer JCV patient, I have taken Tysabri for more than 2 years. Nowhere near 1 in 75 of all comers.

• The 440 number came from Biogen's official numbers in mid-February. On February 4th, the number was 439 pml cases and by March 6th the number was up to 448.
  
• The writer may have taken the study of JCV presence in JCV negative patients (related to the study) and then added in all the other information. That's why the information seems disjointed and inaccurate.

[ru4cats]

Question: Should titer levels of the JC virus level be provided for all those who receive the test, positive or negative?

I am due to go for my JC test in the next two weeks, and I've always been negative. I've asked for the titer level to be provided, but I've been told it's only given for those who are JC+. If a titer level were given, would anything show up for those who are negative? Anyone?

[Marco]

I exchanged a couple of messages with the articles author. She was extremely nice and wanted to ensure the article was correct. She immediately reached out to Dr. Major and is awaiting his response. She also sent me the following information with permission to post it here.

First, here's the relevant text from the study:

"Since the reintroduction of natalizumab therapy in 2006 for relapsing remitting forms of multiple sclerosis (MS), more than 440 cases of progressive multifocal leukoencephalopathy (PML), the central nervous system virus–induced demyelinating disease, have been reported. The highest incidence of PML is approximately 1:80 in patients with a combination of risk factors, including receiving 24 or more natalizumab infusions, a history of immunosuppressive treatment, and seropositivity for antibodies to the JC virus (JCV). The overall incidence of PML in natalizumab-treated MS patients is 1:250, with approximately 11 new cases reported each month."1,2

Here are the studies those numbers came from:

1. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-1880.
2. Kappos L, Bates D, Edan G, et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol. 2011;10(8):745-758.

[Marco]

I have gotten a number of emails from friends concerned about this thread. I do not believe there are radically new PML risks that have been uncovered.

• From the study cited it seems the highest PML risk of 1 in 80 would be someone that is JCV+, has prior immunosuppresant use and has been on Tysabri 24+ months. Biogen has repeatedly stated the information for JCV+ people that have been on Tysabri for more than 24+ months is basically not available. It would stand to reason or inference that if you are: JCV+, have prior immunosuppressant use and have been on Tysabri more than 3 years the risk might well be greater than 1 in 80.
  
• I also believe the % of deaths related to PML is less than 25% and not the 30-50% the article quotes.
  
• The MAJOR consideration from the article is that the JCV test may be less accurate than previously believed. We always knew you could change from JCV- to JCV+ with exposure to the virus. We may now need to take into consider the possibility of a higher number of false negatives exist. I hope additional studies are conducted ASAP. Remember over 123,000 people have taken Tysabri --- the study was limited to 49 people.

Remember, if you have questions about your individual PML risks please contact your neurologist and/or the TOUCH program at 800-456-2255.