Tysabri and JCV

[PaulaG]

Anyone continuing Ty with a JCV titer >1.19? I was taken off and now I'm declining again.

[ru4cats]

I'm JC-, but I know I've read on this website of people with titers over 3 and possibly 4 that continue on Tysabri. They have MRI's more frequently (possibly every month before their infusion) and blood work done every month before infusion, but for them the benefit they derive from Tysabri is worth the risk of PML. I certainly hope some of these posters see your post and respond.

On a side note, IMHO, if my neurologist decided to pull me off Tysabri, I'd be looking for a new neurologist. I firmly believe that the only individual who knows what is in my best interest is me.

[lindaincolorado]

Hi Paula, I agree with everything ru4cats typed I will add that I am now in the indeterminate category-over negative and under positive. I have looked into Rituxin but, it doesn't relieve sx I've been told only Tysabri does . If I EVER have to go off Ty I will probably go to Rituxan (Ocrilizimab trial), but I love my TY

Good luck

[Tomjadg]

I am a 3.5 positive, but I get a brain MRI before each infusion. They told me if I show any signs of PML, I will go directly into the hospital.
Not sure why, as there is no cure or treatment for PML.

I have a 1 in 125 chance of getting it.

[lindaincolorado]

Hi Tomjadg, I'm pretty sure they would do plasmapherisis which would get all the Ty out of your body and the sooner the better.

[Tomjadg]

Thanks Linda. I've read up on that.

[LL60]

I feel the need to put in my 2 cents here.

When I hear that someone's doctor pulled them off of a medication that has been working for that patient with no input from the patient, I get really sad for that patient. And I don't know what to say to them. Obviously you have to trust your doctor. Do you? You have to be a team. And work together. Don't you?

I am on Tysabri. I have been for over 5 years. Before that I was on Copaxone. It had no effect on my MS. Tysabri started changing things at 3 or 4 months. By 6 months my doctors were amazed at the difference. By that first year many symptoms had stopped and I have not had a relapse.
I realize that this isn't the way it is for everyone. Different meds work differently for different people.

For me, it has been almost like a cure.

I refused to test when the JCV test first came out. I wouldn't change anything and why take the chance that my insurance would use it as a reason to take me off of it. My doctor finally talked me into it. I tested pos. Then the new titer/index tests came out. My numbers have always been high.

July, 2013 - 4.1
Jan., 2014 - 3.66
March, 2014- 4.02

This June I changed from the every 4 week schedule to the every 6 week schedule.

Sept., 2014 - 2.4

I changed because I took in information to my doctor about dosing extension and PML rates. This was my choice on information I gathered. Because learning about MS and the drugs for it has become my second job. Because my doctor just does not have the information I need.

I find the longer dosing not to be perfect. Where before I began to get the mind crippling fatigue of MS maybe a few days or a week before an infusion, I now find it hard to get though those last two weeks. I have gone back to taking Provigal even though it cost me $400 for a 3 month supply.

Just a side note. My insurance company was charging me $981 for each infusion (until I hit $2500) and then went to $2,000 an infusion without ever telling me I could get help from Biogen on cost, even though I complained every month to the nurses about how much it was costing me. You guys told me about that and although it was a long tough process due to no co operation from either my doctor's office or my insurance company, I finally did get the help I need to stay on this med. So, you see, I have fought almost the entire 5 years to stay on this med. Because I do not want to even think what life would like without it.

But I guess I will stay at the every 6 weeks because obviously for me anyway, it lowers my numbers. I am very happy to be at 2.4. I hope it will continue to go down. Or another med to get rid of the JC virus altogether comes on the market.

ikT-oo1Pro was in trails in 2013. It removes the virus from your body. Then there are no worries about PML. But since a release came out about it in May 2013 I have heard nothing more about it.

True, once you get PML life is not good. But there are things you can do, so don't think there aren't. First they need to get the Tysabri out of your system. Plasmaphersis (sp?) can do that. There are also antimalarial drugs that have had some effect on the virus. Mefloquine and CYT 107 are two that I have read about.

This situation is not black and white. Positive - no med, negative - yes you can have it. It should be a shared decision. If that's what you want. Researching and trying to make sense of long medical articles is overwhelming at times. Some people don't want this. They trust their MD's and follow their advice. Not saying that is wrong. Because if you make a decision without informed consent and you got some terrible side effect (like PML) not only would you have to deal with that, but you would have to deal with all sorts of issues of guilt and things like that. I shoulda, coulda, woulda type things and thoughts. The stress of feeling like you made a wrong choice would be very unhealthy in itself.

To be taken off of a drug with no discussion with the patient just sits wrong with me. Even if you decide to go off of it, I think you at least still need to take part in that decision.

MS moment. Not sure what my point is. Please anyone who is testing positive with "high" numbers. Understand your risks. But don't just jump off the cliff without knowing if maybe its only 6 feet down and that is something you can deal with. (or something like that )

Thanks for listening.

[Tomjadg]

LL60

Good post. If that is directed at me, I have an excellent relationship with my Neuro. He and my infusion nurse know that I keep up on things, and he has always gone with what I wanted.
My nurse said some of her patients won't even discuss PML or options.

I have gone to 8 weeks between infusions because I feel no difference with the longer wait, and it is possibly better for me.

I just got information on here about a new test done in other Countries (not available here yet) that can show a Ty patient is at risk of PML even 6 months before it occurs.
I will run this by my nurse at the next infusion, and hope we can get the test soon.
There are some problems that have to get worked out yet.

I'm lucky I have good insurance that pays for everything, even the brain MRI's before each infusion for the Neuro to check.
They also paid for a scooter I use at work. That's a whole other story about what a nightmare it was to find a scooter. Some of those companies are such liars.

Good luck

[LL60]

Tomjadg, no was just posting. Not directed at anyone.

Glad going every 8 weeks doesn't affect you. I am thinking I may adjust to the every 6 weeks. It has only been two cycles so far. Fatigue has always one of my continued symptoms, even with Tysabri. It really changes your meaning of "normal."

Did your JCV titer/index numbers go down with the change?

[Myoak]

Always enjoy your posts LL60 and best wishes to all who are extending dose on Tysabri.

What causes PML?

The lack of enough white blood cells patrolling the brain to prevent PML; in that environment PML develops from the JC virus.

With each infusion Tysabri saturation rises allowing fewer white blood cells in the brain to prevent PML.

Extending dose intends to diminish Tysabri saturation and allow enough white blood cells to get through to prevent PML.

Opportunities to decrease PML risk are very, very, limited and too important to ignore.

MS severity may dictate how long dose can be extended. Someone doing really well could go 8 weeks; some could go 7 weeks, 6, 5, or, if battling severe MS may stay at 4 weeks.

Dr. John Foley said, “… there is a striking elevation in PML cases. (The) incidence definitely trends toward patients with lower body weights.”

Why?

“Patients weighing less than 75 kg tend to develop higher plasma concentrations of the monoclonal antibody (Tysabri) over time and are more likely to saturate 95% or more of the lymphocyte receptors that natalizumab targets, exceeding the saturation goal of about 85%.

We think there’s a link between serum concentration and saturation of lymphocytes in general, and that excessive saturation leads to near-complete stoppage of [lymphocyte] trafficking from blood vessels into brain parenchyma." Perhaps "we reach a threshold where we not only impede the cells that are programmed to cause MS, but also the trafficking of the cells that are programmed to kill viruses. We need to figure out what the optimal balance is," Foley said in an interview.

For now, "how we are approaching this is [by] dose-extending high-risk, JC virus antibody–positive populations out to 5-6 weeks, instead of dosing every 4 weeks," as the natalizumab label indicates. It "reduces concentrations in the last few weeks, and saturations decline. It may well be a viable approach for PML risk reduction."

[Tomjadg]

Hi LL60

I'm getting tested for my Titer index in about two weeks, but it didn't change much when I went from 4 to 6 weeks.

Fatigue is always a problem, but I take Nuvigil every day, and that helps.

[Remy9111]

Here is relatively new information about why some people get PML. I did not know about this until recently. Apparently Tysabri alters stem cells that turn into white blood cells -- more of these cells attract JCV and the Tysabri increases the problem (read this as I'm not explaining it well).

http://www.m.webmd.com/multiple-scle...-brain-disease

What was most frightening to me was the discovery that people could test negative for JCV (10 in this study) and still have evidence of JCV viral DNA in these stem cells.

Either we need new or more accurate tests which someone here suggested they recently heard about (I'd like to know more about this apparent test) or we need anti-viral meds that work on JCV.

I do have hope that scientists are learning more about this every day.

[LL60]

Remy,
That is my dearest wish, that they come up with something that gets ride of the JC virus altogether; at the very least ,better tests.
They are working on both. Biogen is funding a lot of it. After all, if they can solve the PML problem, they stand to make billions. Over what they already make!

I did print out the post on the new test and took it into my doctor. I take her a lot of stuff I print off from here or from web sites you guys have sent me to. Love you all for your posts.

My doctor continues to try to talk me out of Tysabri, but so far he is allowing me to continue only because he understands I understand the risks. I am his only patient who is JCV+ still on Tysabri. He is moving his patients to Rituxan. I printed off a ton of information last night and sat up and read about this drug. It is used off label for MS.

It also carries a PML risk, but much lower. Still, I maintain - if you are that one person, you really don't care about the numbers.

If my understanding is correct after wading though stuff that really was for doctors and not me.......Rituxan works by attaching itself to B cells. A certain type of B cells that it thought to cause the damage in MS. This connection destroys the B cells. They explode sending the contends into the blood stream. This is what causes the side effects; like death during your very first infusion. And hair loss, and fatigue and nausea, infections and skin diseases.

It was a little like reading about Tysabri.

It does work well for those it works for. And after the first two infusions, you just get them every 6 months.

But, for now, think I will pass. I will stick with what works and that, for me, has no side effects at all.

[Myoak]

Data from extending time between doses of Ty was collected from 6 MS centers in the USA. After an initial 6 month period of infusions at 4 weeks patients were placed in 4 treatment groups.

1. Standard Dosing (SD) every 4 weeks (n=674)
2. Early Extended Dosing (EED) 4 weeks 3 days to 6 weeks 6 days (n=231)
3. Late Extended Dosing (LED) 7 weeks to 8.5 weeks (n=245)
4. Variable Extended Dosing (VED) those who alternated between EED and LED (n=208)

Results: “NEDA (No Evidence of Disease Activity) including both clinical and MRI criteria ranged from 49% in VED, 57% in EED to 77% in LED. ARR (annual relapse rate) and NEDA were significantly better in LED compared to EED and VED, possibly reflecting selection bias.”

Just a note on selection bias… neuros may have selected their "most well" patients for the longest extension between doses out of caution; fear of negatively affecting their health. In any case, those who extended time longest did the best. Really a surprising finding.

As the abstract states, the hypothesis behind dose extension is dose “adequate to exclude autoreactive T cells from entry into CNS (MS-protective) but nevertheless sufficiently permissive to enable CNS lymphocyte scavenging of JC virus to occur (PML-protective).”

Zero cases of PML occurred in the 684 involved in dose extension.
2 cases of PML occurred in the Standard Dosing group of 674 patients.

This study is ongoing. They note that “We are approaching the 1248 person-years needed to reach statistical significance at 0.05 level.”

If the current pattern holds for a few more months of no PML cases in extended dose then this technique of extending dose will have scientific proof it does reduce PML risk.

Possibly, the present pattern will hold, the study concluded, written up and put into practice by clinicians who are aware of it. And I imagine most are, including the ones who say there are no studies backing the idea of dose extension to reduce PML risk.

It is exciting to think about the possibility of dose extension reducing risk of PML to the point of eliminating it entirely. So far, so good.

Hang in there LL60.

[ru4cats]

Wow, Myoak! You are a wealth of information, and I'm sure I speak for others when I say we all appreciate your willingness to search out new research that will benefit us all!