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Tysabi PML Risk Clarification Needed

Posted: Sun Aug 25, 2013 10:55 am
by larryob98
I am a new member, but we need to decide in the next 24-48 hours whether Tysabri or Tecfidera is the preferred initial course of treatment for my daughter. After exhaustive research, we still have ambiguous and conflicting information on PML risk.

Apparently, the risk of PML for someone who tests negative for JCV antibodies is less than 1 in 11,000. The only way to interpret that statement, since you can't get PML without exposure to the JC Virus, is that in thee cases, the test results were a false negative (3% risk) , and that the patient has been exposed to the JC Virus at some point during the six month period prior to the false negative and for an additional period after the false negative until either the next JCV test or a PML diagnosis. so that the 1 in 11,000 risk is a combination of true negative and false negative patients. This risk apparently does not depend on how long one has been on Tysabri.

If, on the other hand, the patient tests positive for the JC Virus, the risk of PML does depend on how long one has been (past tense) on Tysabri, and for those on Tysabri less than 2 years, that risk is 1 in 1786, assuming no additional risk factors such as the prior use of other immunosuppressants (overcomingmultiplesclerosis.com)

This suggests that at the point at which a patient first tests positive for the JC Virus, past Tysabri use is an issue (i.e., it's not just patients who test positive and continue with Tysabri, but also patients who have never tested positive before the first positive result.

So if you are on Tysabri for up to two years, and you have your first positive JCV result, you already have a 1 in 1786 risk of PML

This, of course, in inconsistent with the risk of patients who test negative not having an increased risk based on how long they have already been on the drug. Since every web page and every medical journal article is written by Biogen Idec, tbere is no variation in the endless repitition of ambiguous language on this point. Any clarification, especially from a published source,would be most welcome.

Re: Tysabi PML Risk Clarification Needed

Posted: Sun Aug 25, 2013 11:28 am
by CaliReader

Re: Tysabi PML Risk Clarification Needed

Posted: Sun Aug 25, 2013 4:28 pm
by bifrostlake
I second CaliReader's post. The Barts and London MS research blog is an excellent resource. Here's is the link to their PML risk education guide: http://www.slideshare.net/gavingiovanno ... -june-2013

I gather that your daughter had a significant first attack to have Tysabri offered as an initial treatment. I recommend that she ask her neurologist how often she will be tested for the JC virus while on Tysabri.

Best of luck on your daughter's decision.

Re: Tysabi PML Risk Clarification Needed

Posted: Mon Aug 26, 2013 6:59 am
by lyndacarol
larryob98 wrote:I am a new member, but we need to decide in the next 24-48 hours whether Tysabri or Tecfidera is the preferred initial course of treatment for my daughter. After exhaustive research, we still have ambiguous and conflicting information on PML risk.

Apparently, the risk of PML for someone who tests negative for JCV antibodies is less than 1 in 11,000. The only way to interpret that statement, since you can't get PML without exposure to the JC Virus, is that in thee cases, the test results were a false negative (3% risk) , and that the patient has been exposed to the JC Virus at some point during the six month period prior to the false negative and for an additional period after the false negative until either the next JCV test or a PML diagnosis. so that the 1 in 11,000 risk is a combination of true negative and false negative patients. This risk apparently does not depend on how long one has been on Tysabri.

If, on the other hand, the patient tests positive for the JC Virus, the risk of PML does depend on how long one has been (past tense) on Tysabri, and for those on Tysabri less than 2 years, that risk is 1 in 1786, assuming no additional risk factors such as the prior use of other immunosuppressants (overcomingmultiplesclerosis.com)

This suggests that at the point at which a patient first tests positive for the JC Virus, past Tysabri use is an issue (i.e., it's not just patients who test positive and continue with Tysabri, but also patients who have never tested positive before the first positive result.

So if you are on Tysabri for up to two years, and you have your first positive JCV result, you already have a 1 in 1786 risk of PML

This, of course, in inconsistent with the risk of patients who test negative not having an increased risk based on how long they have already been on the drug. Since every web page and every medical journal article is written by Biogen Idec, tbere is no variation in the endless repitition of ambiguous language on this point. Any clarification, especially from a published source,would be most welcome.
Welcome to ThisIsMS, larryob98. What a terrible position you are in – to have to decide between Tysabri or Tecfidera for your daughter! INITIAL treatment? It is my understanding that these powerful drugs are prescribed when all else fails.

PLEASE be cautious and do your research. Our member here, HarryZ, has LOTS of good information on Biogen and Tysabri; I urge you to contact him.

Re: Tysabi PML Risk Clarification Needed

Posted: Mon Aug 26, 2013 1:39 pm
by cheerleader
Larry---
Please. Do some more research.
Tysabri was never meant as a first line medication. The creator of Tysabri, Dr. Laurence Steinman, cautions against anyone newly diagnosed using it as a first line treatment, because of the risk of PML. He claims that the risk of one less relapse every three years is "not worth it." He would know.
http://www.iom.edu/~/media/March%2028-2 ... einman.pdf

The JC virus is present in 80-90% of the human population. In those with normal immune systems, this virus remains outside the central nervous system, and latent. The problem with Tysabri and Tecfidera is that they allow the virus to reactivate and enter the CNS.

PML complications are MUCH higher than you have stated...we're only now, in 2013, learning the real risk and odds. Researchers are finding PML in 1 out of 330 people treated with Tysabri
With more than 115,000 patients globally treated with natalizumab for longer periods of time, that estimate number of PML cases is 1 per 330. In patients who test positive for antibodies to JCV, have a clinical history of immune suppressive treatment before natalizumab, and have received more than 24 doses, the number of PML cases is 1 per 90.
http://www.ncbi.nlm.nih.gov/pubmed/23925759

Antibody testing is not an effective means of understanding the risk of PML, because you can test JC- one week, and turn JC+ the next.
Here is a letter written to the NEJM by researchers at the NIH--concerned with the risk of JC reactivation in those treated with Tysabri. They are finding the JC virus present in 35% of patients treated with Tysbari even if they show JC- on the antibody testing.
http://www.nejm.org/doi/full/10.1056/NEJMc1214233

I've written extensivly on the risks of these severe, immune depleting medications on Facebook--I started investigating for my husband, and was shocked at what I found. I hear from patients around the globe who are now dealing with the consequences of these drugs.


Researchers are now discovering the JC Virus activated by Tysabri in neurons of the gray matter in people with MS. The virus does not just show up as a demyelinating disease in white matter. It is creating gray matter atrophy--literally, death of neurons. This brain tissue loss can be seen on MRI.
http://www.ncbi.nlm.nih.gov/pubmed/23868420
http://www.ncbi.nlm.nih.gov/pubmed/23913509

According to e-healthme, a consumer site which compiles reports to the FDA, on July 30th 2013--
665 people have died while on Tysabri.
http://www.ehealthme.com/ds/tysabri/death

2,582 people are currently reported to have PML.
http://www.ehealthme.com/ds/tysabri/pro ... phalopathy

There have been more Tysabri deaths documented, linked to antibody reactions, lethal relapses after withdrawal, and cancer.
We honestly do not know how many pwMS have been harmed by Tysabri. Biogen does not have to report the numbers, and the FDA adverse events page has no way for consumers to access the complete numbers. That's why the e-healthme site is so important.

I wish your daughter well. Look into the first line medications (copaxone, beta interferon) and diet, vitamin D, exercise, nutrition, the vascular connection...do everything you can in these areas first. Dr. Steinman said this about the drug he created, when he asked the FDA to not approve it.
“Do you want to expose someone to the risk of death for eliminating one relapse every three years?” said Steinman. “I say no.”
http://med.stanford.edu/news_releases/2 ... inman.html


cheer