* Downgrading* from Ty to G

[Franzi]

Hi,
after a long journey I now am about to start Gilenya. My ms is very active and different Ms specialists all agreed: I need to be on Ty in order to be *okay*. Well, turns out there is no way I can take Ty due to astronomically high jcv titers.

So Gilenya it is. I was wondering if anybody else had to *downgrade* from Ty to G and what your experiences were (hopefully good!)

I wish you all a nice Thursday, after all it is almost the weekend
Franzi

[LL60]

Franzi,

I am sorry to hear that your MS has gone really active. I hope you are able to continue to do most of the things that you like to do.

May I ask a question? How high are your JCV titers? I would just like to know what your doctor defines as astronomically high numbers. On the Tysabri message boards there is a place for people to share their numbers, but I think most don't feel comfortable doing this and so I have few people I can compare to or relate to or talk to about how we make the decisions we have to make.

[Franzi]

Hi LL60,

Life is still pretty normal, thanks.

My JC titers are 3.78. Does that sound *astronomically* high to you?

[LL60]

I was expecting you to say something like 8.2 or something like that.
As someone who tested at a 4.1; for your doctors to call 3.78 astronomically high is a little unsettling.

Thank you for sharing that with me. Tysabri has been almost like a cure for me. I just can't give it up. To go back to the way things were before - well I just can't do that. But.....of course I do not want PML.

Some days I just don't know what to do. But most days I know I just have to live each day to the fullest and not worry about what might be. I just know what is. And my life is full and wonderful. Only because of Tysabri infusions.

I'm glad you are still able to do your normal things. I have a new normal now after all these years, but it is good. I am trying to make good decisions. It is not always easy.
Again, thanks for sharing.

[cavalier80]

Franzi, Hi. I'm no expert, but from what I've read (and been told by my neurologist) a titer of .378 doesn't sound astronomically high to me. I thought <0.2 is considered "negative", between 0.2 and 0.4 is "indeterminate" and > 0.4 is "positive".
I'm struggling with a similar decision (on Ty, and my last labs came in JCV positive) so can't pretend to be able to advise you! In any event, I wish you, and all of us, only the best.

[Myoak]

Watch those decimals. Big difference between .378 and 3.78.

There is evidence that JCV index of 1.5 has higher risk than 1.3, and 1.3 has higher risk than 1.1, and 1.1 has higher risk than .9, and .9 has such low risk it is comparable in the first 2 years to being JCV negative. So at lower levels the higher the number the more risk BUT there is no data available which says the pattern continues. Beyond the figures above, I have not seen any research which says a 4.1 JCV index has any more PML risk than 1.6 or any other number above 1.5.

At this point in time a JCV index of 1.6 and 4.1 has the same PML risk:

JCV index OVER 1.5 = PML risk of 1 in 1,000 during months 1 to 24.
JCV index OVER 1.5 = PML risk of 1 in 123 months 25 to 48.
JCV index OVER 1.5 = PML risk of 1 in 118 months 49 to 72.

Obviously, talk it over with your doctor.

Perhaps, as time goes on the data will become more refined but for now this what’s available. Yes, JCV Antibody Index Stratifies PML Risk in Natalizumab-Treated MS Patients but to a limited extent.
https://cmscactrims.confex.com/cmsca...Paper1642.html

When all we had was plus or minus test for JC virus everyone positive thought they were at high risk. Now it is known that those who are positive and below.9 have nearly as low a risk as JCV-. That knowledge is the most valuable gained so far about the JCV index.

At this point in time Biogen has not produced data showing that a JCV index of 4.1 has higher risk than 1.6. Below 1.5, higher JCV index does translate to higher PML risk but we don’t know what future data might show. Got to wait for data and let it speak for itself.

New England Journal of Medicine June 6 2013 quote, “a single measurement of viral activity such as a test for antibodies to JC virus may be USEFUL BUT NOT SUFFICIENT (my caps) to assess (PML) risk” End Quote.

High risk is a subjective perception. Less effect MS treatments might be viewed as a high risk of losing present good health and receiving future worse health. Each person is unique and has every right to personal choice. Never easy.

[cavalier80]

Myoak, Are we looking at 2 different scales? I understand how decimals work, and that 3.85 > .385, but I was referring to numbers I read on something you posted on another thread:

"The link below mentions the assay index cut points as follows:
<.20 Negative (JCV-)
.20 to .40 Indeterminate (could be JCV-, or JCV+)
>.40 Positive (JCV+)

Did this refer to a different test or methodology or am I misreading your posts? What am I missing?

[Myoak]

Hi cavalier80,

I believe you are reading and understanding the numbers correctly. The only thing I saw was Franzi mentioning 3.78 and your post mentioning .378 referring to her JCV index number.

Another thought… Franzi said, “My ms is very active and different Ms Specialists all agreed: I need to be on Ty in order to be *okay*. Well, turns out there is no way I can take Ty due to astronomically high jcv titers.”

“MS is very active.”
“Specialists all agreed I need to be on Tysabri”

I understand those statements but then the statement, “there is no way I can take Ty due to astronomically high jcv titers”. I don’t quite understand that statement. I don’t know if a neurologist said it or it is Franzi’s own thought.

The data released shows the PML risk is 1 in 118 with a JCV index over 1.5 and on Tysabri over 4 years; doesn’t matter whether your index is 1.6 or 3.78.

It is perfectly ok for someone to stop Tysabri due to JCV titers but until data proves otherwise, 3.78 is no more of a risk than 1.6 according to Biogen’s numbers.

The index is new and perhaps the future will establish risk is higher with a higher number but only when Biogen has collected and released more data will we know for sure. Maybe they will be able to stratify risk in small increments as they have at 1.5 and below; we just don’t know at this point.

In the meantime, it surprises me that a neurologist could flip position so quickly from MS is very active and Tysabri is required to no way for Tysabri. Switch based on an assumption of higher risk w/o supporting data?

Doctors are as different as patients. Each has, and is entitled to, their own views. I’m not saying Franzi or her doctors are wrong. In the future they may be proven correct. But based on what is known right now, 3.78 has no more risk than 1.6.

I don’t fully understand how a professional could believe a specific treatment was necessary but change his mind based on an assumption of what future data might possibly show.

Cavalier, you appear to have a handle on the JCV numbers. You did say you were JCV+. Remember, if your index number is below.9 the risk isn’t much more than if you were JCV negative. For now, that is the prime way the JCV index is used.

Best to ya.

[cavalier80]

Myoak - Thanks for the clarification. But how does the less than .2 = negative; between .2 and .4 = indeterminate; and greater than .4 = positive mesh with the greater than or less than 1.5 bar?

I guess I thought you're considered JCV + if you test over .4. I tested .44. Are you saying that my risk profile is no different than it would have been had I been tested at .3 (or really any other titer less than 1.5)?

Sorry if I'm missing the point. Written communication is not always the most effective!

[Myoak]

Forgive me for being so dense, but what is your exact question? I continue to believe you have a good understanding but I will try to clarify.

The chart from the link I posted is clear. They give risk for above 1.5, below 1.5, below1.3, below1.1, below .9 for three periods of time in each category. Are you able to find that chart in the link? Just as a reminder, the chart is part of a presentation titled, “JCV Antibody Index Stratifies PML Risk in Natalizumab-Treated MS Patients”
https://cmscactrims.confex.com/cmsca...Paper1642.html


Ok, next item. Different topic. The standard for determining whether a person is considered JCV positive or negative… less than .2 negative, .2 to .4 indeterminate, more than .4 positive. I think it is important to realize that at such low levels it should not be thought unusual to from - to + or back again.

Until 2013 all we had was a test for + or – JCV. So everyone who was JCV + thought they were at high risk. Subsequently, the new JCV index test established that not everyone who is JCV + has high risk. You can see how that information might influence treatment decisions.

Bonus… I recently spoke with a person who has taken Tysabri for more than 7 years, has a JCV index less than .5 and is happy that her index is so low even after a so many years on Tysabri.

Hope in there somewhere I have addressed your concerns!

PS I just checked the link I posted above and was unable to bring it up. When I first posted it I specifically suggested people copy and save it because it could get scrubbed. Biogen is really touchy about what information is shared with patients. If the info was scrubbed, it is the second time I posted links to Biogen charts which have been taken down.

Anyone who saved the chart can verify that the following is what was published:

JCV index less than 0.9 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 0.9 = PML risk of 1 in 3,333 months 25 to 48.
JCV index less than 0.9 = PML risk of 1 in 2,500 months 49 to 72.

JCV index less than 1.1 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 1.1 = PML risk of 1 in 1,429 months 25 to 48.
JCV index less than 1.1 = PML risk of 1 in 1,429 months 49 to 72.

JCV index less than 1.3 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 1.3 = PML risk of 1 in 1,000 months 25 to 48.
JCV index less than 1.3 = PML risk of 1 in 833 months 49 to 72.

JCV index less than 1.5 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 1.5 = PML risk of 1 in 833 months 25 to 48.
JCV index less than 1.5 = PML risk of 1 in 769 months 49 to 72.

JCV index OVER 1.5 = PML risk of 1 in 1,000 during months 1 to 24.
JCV index OVER 1.5 = PML risk of 1 in 123 months 25 to 48.
JCV index OVER 1.5 = PML risk of 1 in 118 months 49 to 72.

Hope this helps.

[frosty123]

have these stats been updated?

Thank you for this.....

Forgive me for being so dense, but what is your exact question? I continue to believe you have a good understanding but I will try to clarify.

The chart from the link I posted is clear. They give risk for above 1.5, below 1.5, below1.3, below1.1, below .9 for three periods of time in each category. Are you able to find that chart in the link? Just as a reminder, the chart is part of a presentation titled, “JCV Antibody Index Stratifies PML Risk in Natalizumab-Treated MS Patients”
https://cmscactrims.confex.com/cmsca...Paper1642.html


Ok, next item. Different topic. The standard for determining whether a person is considered JCV positive or negative… less than .2 negative, .2 to .4 indeterminate, more than .4 positive. I think it is important to realize that at such low levels it should not be thought unusual to from - to + or back again.

Until 2013 all we had was a test for + or – JCV. So everyone who was JCV + thought they were at high risk. Subsequently, the new JCV index test established that not everyone who is JCV + has high risk. You can see how that information might influence treatment decisions.

Bonus… I recently spoke with a person who has taken Tysabri for more than 7 years, has a JCV index less than .5 and is happy that her index is so low even after a so many years on Tysabri.

Hope in there somewhere I have addressed your concerns!

PS I just checked the link I posted above and was unable to bring it up. When I first posted it I specifically suggested people copy and save it because it could get scrubbed. Biogen is really touchy about what information is shared with patients. If the info was scrubbed, it is the second time I posted links to Biogen charts which have been taken down.

Anyone who saved the chart can verify that the following is what was published:

JCV index less than 0.9 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 0.9 = PML risk of 1 in 3,333 months 25 to 48.
JCV index less than 0.9 = PML risk of 1 in 2,500 months 49 to 72.

JCV index less than 1.1 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 1.1 = PML risk of 1 in 1,429 months 25 to 48.
JCV index less than 1.1 = PML risk of 1 in 1,429 months 49 to 72.

JCV index less than 1.3 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 1.3 = PML risk of 1 in 1,000 months 25 to 48.
JCV index less than 1.3 = PML risk of 1 in 833 months 49 to 72.

JCV index less than 1.5 = PML risk of 1 in 10,000 during months 1 to 24.
JCV index less than 1.5 = PML risk of 1 in 833 months 25 to 48.
JCV index less than 1.5 = PML risk of 1 in 769 months 49 to 72.

JCV index OVER 1.5 = PML risk of 1 in 1,000 during months 1 to 24.
JCV index OVER 1.5 = PML risk of 1 in 123 months 25 to 48.
JCV index OVER 1.5 = PML risk of 1 in 118 months 49 to 72.

Hope this helps.