Oh yes, terribly. :rolleyes: She's starting to act like she's going to miss me. I will miss her funny side... It shows once in awhile. I won't miss the rest of it. :eek: Thing is, we'll work together occasionally because her DH and I will have joint projects done out of our own locations. If I do have to spend a lot of time listening to rants from her, it will be billable at a low introductory hourly rate, lol.

It sounds like a few of the patients have had fairly good recovery which is reassuring. Hopefully it will get to the point where they know exactly what to do and can reverse all or most of the damage.

RW --Thanks so much for always keeping us updated on Ty. information. It is great to have you as a resource. :) It sounds like your neurologist is well connected and a good source too.

Yeah...once again...PML update June 19 shows 1 patient. out of USA, 34 infusions, no further information available at this time. I'll let you all know what I find out...

So I got some info today. This is information available to your neurologist and any other licensed physician if they email or talk to Biogen through their medical professionals line. It is not available to the general public or Tysabri patients anywhere that I could find.

I'll just paste what I have.

There is a chart circulating so you can go to it and figure out who is who when it comes to patient # system being used. http://pietynorwit.com/Tytable.htm

On this chart patient #4 is patient #1 after return to market, and is numbered 4(1) All of the patients listed below are post trial patients, so the number they are identified by is the one in the parentheses.

Case nos. 5, 8 and 9 all had novantrone prior to starting Tysabri. 8 and 9 were both in Sentinel, but in the Avonex plus placebo group, and likely had earlier access to restarting Tysabri than the general population.

As previously disclosed, case no. 2 was previously treated with azathioprine, and case no. 3 was previously treated with methotrexate (the latter was the US patient who died after her family reportedly decided not to follow the PML treatment protocol).

Case no. 4 had no apparent risk factors, and was described as of February 2009 as being "communicative."

Case no. 6 also had no apparent risk factors, and as of April 2009 required ventilator assistance. This appears to be the one PML patient in the poorest condition, and the only patient without apparent risk factors to contract PML after 30 months of Tysabri treatment.

Case no. 7 also had no apparent risk factors, and as of May 2009 was described as alert and ambulatory (able to walk 100 feet).

If I hear any more information I will post it here.

Riverwild,

Thanks for the detailed update on the cases and where they stand. Would be nice if they also communicated what courses of steriods if any they were given during their Tysabri treatment period to see if that had any effect.

Chris

Chris, I haven't got any information on steroids administered to people who are on Tysabri who develop PML.

I know there are people here who are or have been on Tysabri and have been determined to be in relapse who received a course of steroids.

As I understand it, as long as MRI shows lesions and inflammation consistent with relapse, a course of steroids may be administered. If ANY lesions are inconsistent with MS lesions (MS lesions are perpendicular, PML lesions may be blotchy, in unusual areas of the brain away from previous lesions, or may be at odd angles from normal MS lesions) steroids should NOT be administered.

I do know that IF a person has PML, is treated with plasmapheresis, and shows IRIS, steroids are part of the treatment for IRIS.

This was one of the problems my neuro talked about, that there are a lot of neuros and radiologists who hadn't ever seen PML because it was almost always seen in AIDS patients who were treated with strong immunosuppressants, but all AIDS patients who are on drugs don't develop PML. ( I went right to the head of my radiology department because he reads my MRIs and asked him straight out and got a very informative lesson in PML and MRIs.)

What we need is a test to check for JC virus, an easy one. Right now it appears that it's a combo of tests checking urine, blood and CSF. 80-85% of the population carries JCV in their kidneys. It's when it's activated into the blood and CSF that it becomes a problem, and in many people it never makes it to the brain.

Some good news to post
 

I just got my MRI results back after having infusion #12. Still no changes--no enhancement and no new lesions. :yahoo: I almost had a serious anxiety attack since it took them a week to get back to me unlike previous MRIs. I finally called and demanded the results! So I guess the Tysabri is working extremely well.

I have also noticed that my fatigue level has improved significantly, back to pre-MS and pre-mono days, and my ability to tolerate heat is almost normal now. It's been 100-102 degrees here for days and I've been outside walking around, traveling, running errands etc. and have had no problems. Wow! :)

Hooray Natalie!! :):hug:

That sounds like my situation. After about a year or so I realized I was feeling a lot better. It happened gradually so it wasn't all that noticeable. I've also had good MRI's all along. :) I feel very fortunate.

Yay Natalie!

Isn't it GREAT to get that report in your hands and read "NO enhancing lesions, NO NEW lesions"?

I've actually got provigil and baclofen stacked up in my med locker now, because things are so good I barely need them anymore!

I'd comment on the heat thing but you all west and south of Maine are hogging it all! We have had rain for 25 days now. It's been cool and clammy, still below 70 today!
I keep praying for a hot sunny day!

Another Tysabri PML confirmed.

June 23, 2009, Outside of USA, 30 infusions

http://phx.corporate-ir.net/External...R5cGU9Mw==&t=1

Wiz, yeah isn't it weird to suddenly realize you just feel better after being on it for awhile? It's been a year and all of a sudden I've just noticed changes--it did come on gradually.

RW, yes the report that said "stable" and "no new lesions" was awesome. All my results get posted online so I can follow everything. Nothing has changed in almost 2 years since I was diagnosed. It makes me think that all my anxiety was for nothing. But that's part of the monster of this disease, right?--mastering the fear about the future. Now I'm trying not to worry about PML. 5 cases in 8 weeks doesn't help.

Link where you can get more detail about the PML cases

Sorry, don't want to get into trouble linking to this

Go to the Elan.com website and poke around in the medical information section.

Cases 8 and 9 had very low JC Virus counts (detected early) even though they were both treated with steriods prior to PML diagnoses.

Interesting stuff in that detailed report. I'll be watching to see what they have to say about the last patient.

I'm wondering if I am being a pollyanna or if I really can feel better that only 2 cases of pml were in the U.S. This month I rec'd #35 and it is a bit nerve racking how many have recently been at around 30-35 doses. BUT, only 1 was at 30+ in the U.S. and the other at 14 and this is out of 20,800 people being on Ty in the States. I get my figures from biogenidec.com, investor relations.
Any input...
Linda

US Cases

May 18, 2009 ~ 22 months started July 07
Oct 29,2008 ~ 13 months started Sep 07

I think we have to remember that there are MANY people who have had long term exposure to this drug as a result of their being in the trials (P1, P2,P3) from the start, who haven't developed PML.

Some of them are at 60+ doses already and I believe a few may be up to 70 doses or better by now!

While they have had drug holidays because of the pull from market, end of trials, etc., they still have a LONG lifetime exposure and didn't develop PML.

I think we are going to see more people going on Tysabri who don't have the risk factor of having been on ANY other therapy when all is said and done. (which is what I was trying to do when the drug was pulled in 2005)

:Wave-Hello: Me again...

I was looking through the excessive list of files in my laptop and found some things that may help folks to understand where we have come from the time the drug was pulled and where they started looking at PML and Tysabri.

The first is the conference call from Biogen Idec the day Tysabri was pulled from market Feb 28, 2005. It's LONG but there's a LOT of info in there.

http://siliconinvestor.advfn.com/rea...msgid=21088871

The second is Lauren Roberts' blog and there's a WEALTH of info there too. I found one patient who sent her a letter who has been on Tysabri since July of 2002 with an 18 month break while Tysabri was off market. That means the poster has been on Ty for a total of 66 doses+-.

"As a study patient, I have been taking Tysabri since July of 2002...That's almost six years. I had to take a 18 month hiatus when the drug was connected to the deaths of two subjects in my study pool. That said, as soon as it was offered again, I jumped at the chance. When I started the Tysabri, I was having difficulty walking. After 8 Tysabri treatments, I was back to running. Only a half a mile at a time, but I slowly worked my way back and played competive (over 35 league) soccer for a summer!
I know that people are worried about side effects. All I can add is that my fellow subjects, if they were going to have side effects, they had them right away...within the first few treatments.
I hate the pernicious nature of this disease--going to bed not knowing how your health will be when you wake. This treatment has cured me of that nightmare."

http://lauren-livingwithms-aolcomlgl....blogspot.com/

Lauren is very careful and checks and re-checks her facts before posting.. She's been involved with Tysabri for a long time and her blog is one of the places I go when I need more info about past info on Tysabri! Thanks to her for her VERY comprehensive blog!

Just FYI...:)

Does anyone know if Vic ended up getting back on Tysabri, or if he evenually moved onto something else? I know his mind is on his wife right now, but I don't know if he ever mentioned a resolution to the $$ situation he ran into with T.

Cherie

This is a great blog, thanks for the link. I like the quote she has on there (from someone on a message board) that basically sums up what I've been feeling about the CRAB drugs:

As far as the PML risks go, even though I'm not in a place where I'd consider Tysabri, I still think that the issue is blown a little bit out of perspective. To compare, I know that this is another thorny issue, but compare to childhood vaccinations. Statistically there are higher risks of "adverse events" from those yet most of us still vaccinate our children, even though the risk of contracting those diseases is relatively small. With MS there is a sure decline in one's health vs. a low risk of a major complication. Given how well the drug works for most people I totally understand why people choose it. Being new to this disease I also really appreciate the fact that this type of drug even exists!

I don't know if he ever got back on Tysabri, Cherie. I've heard as much as everyone else has from Vic, that he is busy with his wife's recovery and that's about it. I am sure when he can update us he will.

Thanks PL! :)

I am not sure what your experience is with your neuro, but most of us were handed a bag of literature and tapes and told to go home and call back when we chose a drug. I don't know of any other disease where they do that.

Many folks are on one or another of the "CRABs" For some, their choice works very well. For others, they run through all of the choices. Obviously, on this Tysabri thread, there are people who Tysabri is working for, so we can be called "Tysabri cheerleaders" There are also a lot of folks who have been here who, for one reason or another, have chosen to stop Tysabri and moved on to another therapy, or chosen to go "naked" and not choose anything for now.

One of our objectives when we fought to get Tysabri returned to market was to allow us the opportunity to make an informed decision and choose the drug we wanted.

This board exists to support people and give them all the information we have to help them make an informed choice. They can talk to people who are on each of the drugs and assess the risks involved for each of them, the ease of use, the side effects, and hear others' stories on the good and the bad.

Each time a new report of PML comes out, folks who are on Tysabri each have to make the decision all over again in their head, to continue taking Tysabri or to make another choice.

Regardless of what anyone's personal choice is, we support them in their decision.

I for one, have chosen to stay on Tysabri once again, after the latest case of PML that was reported, with the information I have received here and from other sources.

Let us know how you are doing and we will support you in whatever therapy you choose! :hug:

Thanks to Komokazi for the heads up!

Info on the 10th PML case is now on Elan's site.

In brief:

On 23 June 2009, tenth confirmed post-marketing diagnosis of PML in a 27 year old male in the EU with a history of MS. The patient had previous exposure to interferon-beta, Copaxone, and IVIG. The patient received 30 TYSABRI doses between January
2007 and June 2009. Symptoms began with right hand weakness. MRI scans
revealed new lesions in the left motor and parietal cortex. PCR of CSF
returned 250-500 copies of JCV. Plasma exchanged started. Patient is
reported to be stable according to treating physician.


More good info: PML lesions do NOT enhance with contrast on MRI. I think I knew that but forgot it, and I may have posted it before. I just woke up and haven't finished coffee quart #1 yet!

thank you for the support.... nope, I got no information. Just a quick "debriefing" in his office and an ultimatum-of-sorts to call him in a week with my decision. I didn't really demand any info, partly b/c I was peeved at his attitude and didn't want to prolong the visit, but mainly because I figured all I would get is the same marketing info I can download directly from the manufacturer's online.

It's exciting to hear of people that are good responders to any drug, really.... a lot of times you just hear the stories of people who the med works only so-so for them, or not at all, which is unfortunate. It's reassuring that I have come across a few good positive stories for the ABCR/CRAB drugs (where the heck does that second acronym come from btw?)

A question on PML-- is it fair to say that this is a disease that comes about as a result of immune suppression or is the reason not very well understood yet?

Also, a question on Tysabri-- does it impair one's immune function in a general way, or is it more targeted to the MS? In other words, does one have a higher risk of coming down with common viruses/bacterial infections? And does one tend to stay sick longer?

Thanks!

Hi PL,

I've heard of other people having problems with infections, but I am one of those people who never gets sick. I've had a run in with salmonella and a ruptured appendix but the first was due to something I ate and the second was something that anyone could have!

When my doc does my bloodwork, I have slightly higher than normal WBCs, and he says that is from all the T cells milling around because they aren't getting into my brain anymore. He says all it does is block T cells from crossing the blood/brain barrier and damaging myelin, and that it doesn't block all of them but enough are blocked to stop damage.

I think that not enough is known to make a stand on what actually causes the JC virus to activate and cross the BBB. 80-85% of the population of the world carries the JC virus in their kidneys and it is usually dormant. PML has been seen in people with AIDS who are immune suppressed, in people who are treated with Rituxan, Tysabri, Raptiva, Cellcept, Methotrexate, Mitoxantrone, chemotherapeutic drugs, corticosteroids and some transplant drugs.

Because of the PML cases associated with Tysabri, more has been learned about PML than ever before. It was previously known as a fatal disease. Now, with plasma exchange along with treatment with mefloquine or mirtazepine, and steroids if IRIS develops, people are living after diagnosis of PML.

Reports on patients diagnosed with PML after Tysabri shows that most of the patients diagnosed so far are still alive. Some are doing well. Some of the earlier people are very disabled. The key seems to be increased vigilance and reporting ANY symptoms to your doctor. Since not many people are relapsing on Tysabri, when signs of relapse are seen, the new norm is to suspect PML first and vigorously test for it with blood tests, spinal taps, MRI, discontinuing Tysabri and further treatment if necessary. It COULD be just a relapse, but no one takes that chance now.

Sorry to be so long-winded but you did ask...:p

The history of the CRAB drugs' development is a sad story in the treatment of MS patients.

If one were to look how first Betaseron, then Avonex, Copaxone and to a lesser extent Rebif, were tested and approved for MS, it is yet another classical story of how big pharma pushed these treatments into hugely revenue producing medications.

But this is what happens when there was absolutely nothing to treat MS prior to these drugs showing up. Stats that were manipulated to show far better results than actually happened while the severe side effects were constantly minimized.

It is not surprising at all that Tysabri has been embraced by many of those who use it because for the most part, the patient doesn't have to go through the bad side effects that many of you know all too well.

It will be interesting to see what happens to Tysabri when the oral medications hit the market. And this will likely happen in the next couple of years.

Harry

RW: Thanks for all the useful information once again. Correct me if I'm wrong but AIDS the disease leads to the weakened immune system (low T cell count) not the drugs patients take. These patients don't take immunosuppressant drugs because that is counterintuitive and dangerous--hence, the effort to find antivirals that could wipe out or put into remission the HIV virus.

Just to add to what RW has said, while the idea of PML worries me, mostly when these cases arise, I am also planning to stay on Tysabri for the near future. I have been on it a year now and just recently I have noticed a big change in how I feel. It kind of snuck up on me. ALL my fatigue is now gone. I feel like I did before I got MS. I sometimes forget I have MS which is such a nice thing. It really is remarkable! :) I can see why people pushed for this drug to be offered again as an option. Anyhow, for now I am quite happy and feeling more assured that people are surviving PML and not all are seriously disabled.

You are correct, Natalie! :)
I was in a rush and trying to get everything down before work and I got lost and didn't notice the error! :o
I was thinking immune suppressed but I was ahead of it already trying to remember the names of the drugs associated with PML.

Thanks for the reply ... guess I'll wait till he comes back to this thread, if that's what he is on.

Great summary, RW.

Cherie

Tysabri works great for many of the people I know--which is about 10. The PML risk is there, and one should assume it fatal when it occcurs. The risk is higher for those who have received mutiple immune modulating therapies, especially when they have been given in close temporal proximity. If two immune modulating ("traditional") therapies fail to prevent flare ups then tysabri should be considered next along with other treatments--with the understanding of the risk of PML.

Which DMD are you currently taking, Mdot?

Kelly, I think MdotDdot is a visiting MD?

Welcome MD, please do introduce yourself. I have read some of your posts and you seem to be knowledgable about Meds, Sides and symptoms.

Are you also ill and need support? We are here for you, as all others, and welcome your special kind of support, as well.

Again, Welcome..:hug:

Hello MdotDdot and welcome to the Tysabri thread.

I have to disagree with some of your post.

The data since Tysabri's return to market shows that PML is NOT necessarily fatal anymore. PML CAN be treated. When caught early, there may be little damage. The key to preventing damage due to PML is VIGILANCE, and those of us on Tysabri are pretty vigilant by now, and so are the neurologists prescribing Tysabri, and the infusion centers administering Tysabri.

As to traditional therapies, who should choose? We get sent home with a pack of info from the drugmakers, and told to come back when we pick a therapy. It's OUR choice. It should BE our choice no matter what. I planned to go on Tysabri and was scheduled for my first infusion when it was pulled from market in 2005. I hadn't taken any other therapy prior to that and the ONLY reason I agreed to do Copaxone was because MY CHOICE was no longer available and Copaxone seemed to be the least obnoxious of the drugs available.

I waited and worked to get Tysabri back on the market, while suffering from relapse after relapse on Copaxone. Copaxone obviously wasn't working for me, so it would be considered inadequate. When Tysabri returned to market, I went on it as soon as I could get on it. I haven't looked back since.

It's my brain. It's my body. I am an intelligent person and I can weigh the risks and benefits using the available information. I would still make the same choice today, to use the most efficacious therapy available to prevent relapses and slow the progression of disability.

Tysabri is prescribed as both first and second line therapy. The FDA clarified that back in 2006. Tysabri is generally recommended for patients who have had an inadequate response to or are unable to tolerate alternate MS therapies. I cannot tolerate losing my brain to this disease, nor can I tolerate drugs marketed to people with MS that, at best, give the patient a 34% efficacy rate.

I haven't had a relapse since I started Tysabri and it's been over two years now. My MRIs are tremendous. Not only do I have no new lesions and no enhancing lesions, many lesions seen previously are reduced in size or gone completely. My vision is back to pre-diagnosis levels, my spasticity and fatigue have been cut to 1/3 or better than where they were before Tysabri. My thinking is clear and I can read a book again without having to re-read every paragraph I previously read. I can retain information again. I'm not dizzy or walking like someone who is intoxicated. I can drive. I can work full time and work more than one job. Time is brain. So far, I'm holding on to mine in what I consider to be the best way that I can.

So, do you have MS? What therapy are you on? How's it working for you?

I'm just stopping in to say "Hi" and hope everyone is still doing well on their Ty journey.

I was so bummed when I got NABs with Ty. I have now been on Copaxone since March 22nd, and the fatigue is horrible! That was the one thing on Ty I noticed the most, I just wasn't so dang tired all of the time!

I don't have a lot of hope that when I have an MRI next March that I won't have many more lesions. But I've run out of drug options for the time being, and hopefully the C will get me by until the orals come out.

The good news is that I have such a good layer of fat all around I'm not having any skin problems with the C ;)! And no relapses, but then again, I didn't really on any of the drugs, just more lesions.

I feel a little bad because I went to a meeting with a doc from an MS center in Colorado, and he said he would have never changed me off of Avonex just because the MRI showed new lesions. He made the comment that you treat the patient, not the MRI! An interesting way of looking at things.

But it is what it is. Just wishing you all the best with Ty, and know I'm jealous!

Hi Mom!

Good to see you again. Glad to hear you aren't having any skin problems with Copaxone. I think the lumps and itching were the worst for me when I was on it.

Are you treating the fatigue? Provigil worked miracles for me, and it still does when I need it to.

Good Luck with your treatment and let us know how you are doing!

Hi 4boysmom - -Nice of you to stop in and say hi. We miss having you around! I hope the Copaxone works for you. :)

I had #13 yesterday. It got delayed a couple of days because I had the chance to be interviewed on the radio for my profession at the last minute and the only time they could do it was during the Tysabri appointment on Monday. So I thought it was worth it to delay!! I will go back to the regular schedule next time (25 days from now).

This was my second time at the new facility and it is a dream to be here. :) Once again they ordered lunch for me at Subway and delivered it right to the chair. The infusion was slowed down even more -- to 2 hours. Whoohoo! I feel even more able to recover afterward (just fewer side effects). Everyone is so friendly and caring at this place -- I guess I'm just not used to that given the horrible experience I had at my MS clinic's infusion room.

I did learn that all new people going on Tysabri in my MS clinic are having their blood sent to a doctor at the NIH who is working on a vaccine for JC virus. I guess the director of my clinic is helping out this researcher. I wish I could remember the name of the doctor/researcher but next time I will find out. I thought this was quite interesting. I guess it behooves Biogen/Elan,to do everything in their power to figure out how to eliminate the PML risk from their "blockbuster" drug Tysabri so they can keep the income flowing in. As it stands now they are way under the numbers of people they predicted would go on this drug by 2010.

Just to add in response to the conversation generated by MdotDdot: There are people who will choose Tysabri as a first line option. And there is nothing wrong with that. I was mostly treatment naive before I went on Tysabri. I tried Rebif for only 2 weeks. The depression was so severe in that short time I had to stop the drug given my long history of depression. I tried copaxone for 6 1/2 weeks and the anxiety, insomnia, fatigue, and general malaise I experienced was intolerable and I couldn't do my job. I suppose I could have stuck it out even longer on the copaxone to see if the side effects went away but I decided that my quality of life was important to me. The side effects of those CRABs really do suck!! I came to realize that I also wanted to be as aggressive as I could in the earliest stage possible so I chose Tysabri instead of toughing out the Copaxone. For me the benefit outweighs the risk. I can forget that I have MS. I do not have any MS symptoms nor have I had a relapse.

Thanks for the kind words, guys! I do try to take 100 mg of provigil most working days, but I don't notice a difference. Even when I first started, it did help me stay more alert, and it still does that, but my eyelids feel like they weigh 100 pounds most days.

I'm sure some of it now is just the heat. If I take more provigil, then I don't sleep at night, which I also figure contributes to my fatigue. I just didn't have these problems on Ty! I did on Avonex and Rebif, along with Copax now, but I don't recall that entire year on Ty complaining of fatigue so much.

Well, I've talked DH into taking me to dinner, so away I go! Then home to bed and it is only 6:00 p.m.!

Hiya Natalie,

:yahoo:
Glad to hear that things are going well with the new infusion center. It sounds much better than what you posted about your previous place!

I'm happy to hear that slowing the infusion is working for you too! Sometimes they overlook the simplest things, and make everything more complicated than it is. I found that out when I had the pinpoint itches and we re-mixed the bag and voila!

Good to hear that there's some investigation going on to prevent PML. I've been watching for something like that to start being news'd around. I'd love to hear more when you get more information.

I'm no scientist but I still believe that it's not the Tysabri, per se, but the immune system and what the patient was exposed to before Tysabri, or the dose of Tysabri relative to size of patient. I still can't believe that the dose works the same for someone who is 5 feet tall and 90 lbs. and someone who is 6'2" and 220 lbs. and I haven't seen any stats on that yet. It could turn out to be something entirely different but like slowing the infusion or re-mixing the bag, everything should be investigated.

Biogen reported no newly diagnosed PML patients today on their minimal information release page.:)

No new PML cases is all the information I need.

Biogen reports earnings this week and maybe they will talk about their research efforts to detect PML earlier and to identify risk factors for PML.

Chris

I wonder about the weight too. I remember I read something about weight and clearance from the body in the insert. I went searching and found what I was looking for from Elan.

http://www.elan.com/Images/EMEA%20SPC_tcm3-14693.pdf

"Only body weight and the presence of anti-natalizumab antibodies were found to influence natalizumab disposition. Body weight was found to influence clearance in a less-than-proportional manner, such that a 43% change in body weight resulted in a 31% to 34% change in clearance."

And this from NIH.

http://www.pubmedcentral.nih.gov/art...?artid=1936307

"Analysis of pharmacokinetic data from Phase 2 trials and population modeling indicated that natalizumab clearance was only weakly correlated with body weight (over the range of 40 kg to 100 kg), but that natalizumab exposure (area under the plasma concentration-time curve and maximum plasma concentration), increased in proportion to weight despite the use of weight-based dosing (Bennett et al 2002; Rudick and Sandrock 2004; Biogen Idec Data on File). However, the effect of patient weight on natalizumab clearance and exposure was within the typical inter-patient range and was not considered clinically relevant. The 300 mg fixed dose selected to achieve maximum α4-integrin saturation was expected to produce acceptable pharmacokinetics in Phase 3 trials (Table 1)."


Essentially it sounds as if weight does make a difference but it is not "clinically relevant." :confused: If that's the case I have to wonder how they know with certainty it is not relevant?