Another PML Case in Europe, and US PML Patient #6 Dies
 

For those who don't follow the Tysabri thread, RW announced the 7th patient with PML had been discovered in Europe:

Also, the 6th patient (or 3rd since the re-introduction of the drug), from the US, has died recently:

The ratio of PML cases now appears to be 7:9500 (or 1:1357), for those who've been on it for 18+ months. Still slightly less than the 1:1000 they predicted.

Cherie

The thing is that most patients are not monitored closely enough, according to my neuro. He comes in and speaks with me every month. They're very careful at his office. Many patients don't see a doctor each month and that troubles him. It troubles me too because they need to watch for signs of PML looming. It shouldn't just be a cash grab for the doctors and centers infusing it.

I had my 21st infusion today and he gave me the news of the most recent death.

It is clearly still a better risk than they predicted, at least so far, so I don't see why this news would scare people into a different decision.

And I agree that people are probably being watched like hawks, especially as the number of cases increases. The ratio of 1:1000 was predicted for over 18 months of use, and we are getting to the point where there are a fair number who are reaching that timeline now . . . so no doubt the doctors will be more vigilant and/or hyper-sensitive to any news that comes out over the next 6 -12 months.

Originally it was thought that this Florida woman was sent home and doing ok, but then she dies! :eek: To date no one has died post-marketing, so I think they hoped that that wasn't going to happen if it was caught quickly enough under TOUCH safety protocol.

There are only 9500 who've been on it long enough (and a large % of those were in the trials), and who've come down with PML . . . so I don't think they claim to have any clear patterns emerging. At this point it seems to be luck of the draw whether we will get PML, and/or whether we will live through it.

But, like I said, everyone on it already accepts that risk.

Cherie

"Biogen has hoped that PML could eventually could be a "survivable adverse event." "

^^ This line REALLY bothered me from the article. 'Adverse event'? You kidding me? It's almost like they're downplaying the severity of PML... at least that's what I took home from their choice of words.

My neuro insists that all of his patients on Tysabri undergo a spinal fluid analysis every six months, in an attempt to detect activated JC virus.

He's pulled a number of patients off of the drug who have come up positive for the activated virus but had not yet developed PML.

I'm on Rituxan, another drug associated with PML. I should be scheduled to have a spinal tap for spinal fluid analysis purposes sometime in the next few weeks...

Apparently it is "survivable" if you have HIV or AIDS but not in this situation? (I remember reading that somewhere I think or my neuro told me.)

It isn't really something you recover from, not like you can go back to any semblance of your life before PML in these cases, if you happen to survive.

"Survivable adverse event" doesn't sound as tuned out as "treatable side-effect" . . .

"Patients on the drug are now closely monitored and four cases of the often fatal infection have occurred since its July 2006 relaunch, but the death may quell hope that PML could be a treatable side effect of the drug."

Like Wiz said, it's not like a person has a chance of EVER recovering from the damage that PML causes . . . :cool:

Cherie

While this doc should be commended for following his patients so closely we know that he would be in the minority at this level of concern. What is disturbing is the fact that he has stopped givng Tysabri to several of his patients who are showing activated levels of the virus. You start to wonder how many other patients may be in this category and don't know it!

Harry

Has the notion of testing spinal fluid in those taking Tysabri come into discussion as part of the TOUCH (or whatever) programs?

It would only make sense to me that IF looking for a pre-cursor to PML is possible in the spinal fluid, that this be part of the routine of monitoring.

(I know nothing about the background of Tysabri, but I'm just shooting this one out there for perhaps someone to respond to, because now I'm curious!)

Here's a link to a PDF my neurologist's research on this issue. It should be of great interest to those following the Tysabri saga...

http://msrcny.org/pdfs/JC-BK_virus_in_MS_4-08.pdf

As Marc pointed out, some prescribing neurologists are attempting to be much more proactive in this regard than others are.

The problem is that there is no fool-proof method for determining if someone has PML, even when it is the person is highly suspected (showing obvious clinical signs) of having it.

For instance, in the case of one of the European patients who came down with PML, he was originally suspected of having it, so his CSF was tested. The result came back negative, but his doctor didn’t trust the results and treated him with plasma anyway.

When he continued to decline, he was given another CSF test and it came back positive this time:

http://www.sec.gov/Archives/edgar/da...14958ke8vk.htm

Cherie

And, I doubt he is the only one doing this . . .

"Suspected PML Cases For Biogen, Elan MS Drug Not Alarming
12-08-08 1202ET

By Thomas Gryta

Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Tysabri, the controversial multiple sclerosis drug sold by Biogen Idec Inc. (BIIB) and Elan PLC (ELN), caused 22 suspected cases of a rare brain infection through early October, according to reports filed with the Food and Drug Administration, a level deemed unalarming by physicians.

Biogen didn't dispute the figures but has declined to disclose the number of suspected cases, arguing it doesn't help physicians and patients and doesn't measure the true risk for progressive multifocal leukoencephalopathy ...

Wall Street, though, has sought more information about the number of suspected PML cases in order to better assess the drug's future prospects, considered key for both companies. Analysts and investors have questioned Biogen's reticence to disclose more.

Dow Jones Newswires compiled its number of suspected cases by reviewing 3,441 Tysabri adverse event reports filed by doctors and Biogen between July 2006 and Oct. 6, 2008. The 22 suspected were determined to be negative for PML, except for two confirmed in July. The third confirmed PML case was announced after Oct. 6. ...

As of Sept. 30, more than 35,500 patients use Tysabri, with 9,500 patients on it for at least 18 months and 3,700 for more than two years. The timeline is important because two patients with PML in 2005 were using the drug for more than two years. This past summer marked the two-year anniversary of Tysabri's re-launch, raising Wall Street's anxiety over PML-related news. ...

Klein is comforted that PML may be treated with plasmapharesis, a process that removes large molecules from the blood, speeding up Tysabri's removal and allowing the immune system to fight the PML infection.

All three recent PML cases were treated with plasmapharesis and have survived the often fatal condition. Biogen reported that the first two have shown improvement, while the third patient "seems to be doing well."
"It is starting to raise the question of whether PML associated with Tysabri could be a survivable adverse event instead of an almost fatal disease," said Naomi Aoki, Biogen's spokeswoman.

The FDA database also shows 160 deaths among Tysabri patients, but Biogen reports all deaths to the FDA database regardless of any apparent relationship to the drug. The company asserts there is no evidence of a mortality issue.

Physicians note that death is not a common occurrence in MS patients, but that some physicians use the drug as a last resort for advanced MS patients, which may distort the data.

Heightened Vigilance
The FDA said it subjects Tysabri to heightened vigilance because of the PML risk and the previous market withdrawal. The agency stressed that it assesses all serious adverse events reported with Tysabri.

Nonetheless, observers - including the FDA and Biogen - note that the adverse events reporting system may not represent an accurate number of suspected PML cases. More cases are likely suspected, and then dismissed, before getting documented in the database.

"The challenge is that the symptoms of PML are very subtle and hard to distinguish from MS," said Robert Fox, medical director at the Mellen Center for MS at Cleveland Clinic.

Fox said it is "not infrequent" that he holds use of Tysabri in a patient on suspicion of PML. He and Jeffery each have consulted for Biogen in the past.

Citigroup analyst Yaron Werber believes disclosing the number of suspected cases helps Wall Street more than it does physicians or patients. Antony Page, who teaches corporate law at Indiana University, notes that Biogen's lawyers have likely formed an argument that disclosing the suspected cases isn't material information.

Meanwhile, Barclays Capital analyst Jim Birchenough contends the number of confirmed cases is likely higher, arguing that Biogen's strict policy on how to confirm PML keeps the number lower.

"When physicians suspect PML and you can't rule it out definitively, I think that is something that should be disclosed by the company," he said.
Biogen disagreed and remained confident that it hasn't missed any confirmed cases of PML. In the meantime, the company is hoping to establish a regular system to keep Wall Street updated.

"Our goal is to move towards a more quarterly update," Aoki said. Biogen will handle each case individually and continue disclosing cases by filing with the Securities and Exchange Commission if it provides insights to physicians or has news material to investors.

http://www.smartmoney.com/news/on/?s...7-1202&print=1


NOTE:

**"Klein is comforted that PML may be treated with plasmapharesis, a process that removes large molecules from the blood, speeding up Tysabri's removal and allowing the immune system to fight the PML infection."*

The problem with that is plasmapharesis (which "speeds up Tysabri's removal") is suspected of causing IRIS in some people who have PML . . . which is potentially as serious as the initial PML. :cool:

Cherie

Reprint of Tysabri thread post
 

This is a reprint of my post in the Tysabri thread -- it belongs here as well.

Why is it that every time someone gets PML and/or dies from it after taking Tysabri, there are others in this forum who feel the need to imply "I told you so!" This is very insensitive and not helpful to people taking Tysabri. :( What new information do we learn each time? Not much. But we get the same old tired debate where those on Tysabri are made to feel like dummies being duped by Biogen. Life with MS is already hard enough. And it's the Christmas season so let's be supportive of one another and thoughtful about what we say.

Hey there Natalie8, I respect your perception on this but if it helps at all, I'm not hearing anything resembling an 'I told you so' vibe from anyone. On the contrary, Tysabri discussions on this forum seem pretty measured, which - considering we're all in this MS thing together - is a nice change from what seemed more typical on several boards some months ago.

Anywho, hope it's okay to share my two cents on this one. :)

Natalie,

I don't think anyone is saying "I told you so". I think some people get really irritated with Biogen, since they haven't always been popular as far as putting patient safety before profits. There are quite a few companies that are like this of course, but Biogen has taken a lot of heat for it, especially as far at the Tysabri trials and such. My neuro feels the same, and when he tells me about another person with PML, he isn't saying "I told you so" but just wants me to keep it in mind and make sure I report any changes to him so I can get checked out just in case.

I know we seem to go over it a lot in posts though and it gets wearisome because many people are posting about the same topic each time, usually in several posts on each forum. I think the reason for that is because we care about each other and we want to make sure it's well known so the people who don't really pay attention to the MS news, OR those who aren't checked regularly by their neuros (and on Tysabri) will take heed and remember that they need to be careful.

Try not to worry... :hug: :hug: :hug: ... we know we're taking the best medicine for us.

Hi Natalie,

You seem to be genuinely interested in hearing answers to your questions, so I will try to respond, at least from my personal perspective.

Firstly, if there wasn’t this controversy about Tysabri, I suspect most everyone with insurance (including probably myself) might try it. It is at least as effective as our other options, it is much more convenient, and there are less general side-effects. However, it is the fact that it is still considered too dangerous for some people’s/doctor’s liking that it hasn’t already stolen most of the entire market. That is also why there is constant conversation about it . . . there are still many people & medical professions who are on pins and needles about how safe it is, and may “appear” to be waiting for the other shoe to drop.

I empathize with your frustration about the constant discussion that goes on, however I feel it from an opposite point of view. From my perspective, the question should be . . . “why is it that every time someone gets PML and/or dies from it after taking Tysabri, there are others on this (and/or other) forum(s) who feel the need to” ... belittle or deny every fact associated to the published information? Clearly this is not very helpful for the VAST majority of PwMS who are still trying to weigh the true risks on this drug.

I understand why those on the drug don’t want to hear what they perceive as “negative” news . . . but “you” (current takers) have already decided Tysabri is worth the risk, and it is presumably working well for you (for which I am very, very glad!). You have already fully evaluated all the pros and cons, and are on top of all the news as it is published ... which is great. However, “you” are still in the minority on the forums, and there are many that have not yet concluded one way or another whether we may want to try Tysabri. Some have been patiently waiting the 2+ yrs to see what comes out of the woodwork, and THEY want to hear the latest news, even IF you don’t.

So, the discussion that ensues, when “negative” news is released, is mostly for the benefit of the people who haven’t made a decision on whether they want to try it yet, and/or for those who might change their mind knowing there are bigger risks than perhaps they wanted to believe when they made the decision.

As it is, much of the information that can be readily googled on Tysabri is outdated within a month or so, i.e. many articles still say “no PML deaths” since the reintroduction, or “only two cases of PML in Europe since the reintroduction”, etc. This can be very confusing to someone who is trying to weigh up the current news.

What has annoyed me personally though, since the very first questionable event with this drug/company, is there have been a handful of very vocal people (including those who are not even on it) who continuously deny every unfavorable event or issue surrounding this drug. Comments such as:

- “she didn’t really have MS” (so therefore that Tysabri/PML case doesn’t count), or
- “he took an immunosuppressant or immunomodulatory drug in conjunction” (and that’s the ONLY reason he got PML), or
- “there is a rumor that he might not have really had PML” (so we won’t count that one either), or
- “those people in Europe aren’t on TOUCH” (so “perhaps” the PML wasn’t caught early enough... “oops”), or
- “she might have died from another treatment” (even if it THAT treatment was only required to combat the PML caused by Tysabri)
- Etc.

Yet when someone tries to clarify with a contrary perspective, or when the truth ultimately comes out, people jump up and down saying “why so negative?:(” or “why imply I told you so?:(” My question is, “why bother trying to deny the news to begin with?” Why not just sit back and wait to see if the crux of any new Tysabri news proves false (which in my experience, 99.% of the time it does NOT), then clarify it (with LINKS) later? :cool:

Frankly, I’d much rather that Tysabri proved entirely safe, and that all the reported cases of PML were just some “fabrication from some competitive rival”. Time and time again though, the people who have claimed the news is just “speculation” have proven dead wrong . . . so of course there are some of us who more than fed up with that merry-go-round. This has been going on for YEARS . . .

The most valuable publicity that Tysabri gets is through “word of mouth” by vocal proponents, IMHO. Unlike many other drugs, the marketing plan for this drug is clearly very reliant on people down-playing serious side-effects, suggesting that any news or comments are “misleading”, by implying bogus statistics, by comparing Tysabri to other “dangerous” drugs, etc. There are even some forums (especially those sponsored by the pharma companies) that have gone as far as BANNING anyone who confronts any misleading Tysabri-“positive” statements!!

We have probably all read comments about how one drug or another has affected someone negatively. So what? . . . are we not supposed to talk about these things because it is not being “thoughtful” or “sensitive” to people who are taking it?

It takes two to tango on these discussions, Natalie . . . and as much as some (current and prior) “takers” seem to think they are the only one’s entitled to express their thoughts, “you” are obviously going to be at least somewhat biased. For the benefit of those who have yet to make a decision on this drug though, IMHO it is important to encourage rights of ALL to communicate openly about the pros and cons.

Cherie

Cherie, I agree with you. There is nothing wrong with discussing or even debating the Pros and Cons of a particular drug....This is how we learn and are able to then make informed decisions.

The Tysabri check-in and Information Thread is not the place, however, for these kinds of discussions. Riverwild started that thread with the hope that it would be a place to report your experience with TY and to receive support from like peeps on TY.

Legitimate, linked, info and updates are posted there, so they are not sticking their heads in the sand. If a Newby, who is thinking about trying TY, reads that thread, they are not lead astray, but can see the facts and are incouraged to consult their Docs. Some, who have had to get off of TY, have also reported there, so newbys will see both sides, without the unnecessary Bickering and naysaying.

JMHO Cherie, and I'm sure we can all respect that.

And I agree with you too, Sally, in principle. That thread is not the place for speculation . . . HOWEVER, “speculation” goes both ways; “positive” and “negative”.

For instance, if someone “alludes” to what would be deemed as positive “speculation”, i.e. like “There’s talk that X really have PML” (even though Biogen has already filed a K-8 admitting it), or “6 of the 7 cases of PML don’t count” (with sufficient hard EVIDENCE to the contrary). . . it is not only fair game, but also IMPORTANT, that a rebuttal be written right where misinformation was “announced”.

Those “positive” comments are seldom accompanied by legitimate (or ANY) links either, and the information can be very misleading for people who might look primarily to that thread for the straight goods on this med.

My suggestion would be (and what I have been mostly trying to do), is post a link to another thread where open communication should be encouraged. However, that doesn’t necessarily work out either . . . because a thread-started can apparently just “request” to have a thread locked up if their “positive speculation” is challenged.

How can there be open communication, for the benefit of those who want to evaluate ALL perspectives, when there is this level of defensiveness?

What is the answer?

Cherie

Good point, Cherie. There should be no speculation at all in that thread...Just Facts and Support.

Realistically, there will be words of speculation, that creep in, but it should be stated as such, so that others don't think it's a real fact.

There, all fixed, so, I double dare you to stay out of there....unless you are lending support..:p

If you look back through my postings on that thread over the past year, the largest percentage of comments are in response to someone's questions or concerns ~ which are not NECESSARILY specifically related to the drug. I have said "itching may be as a result of X, rather than Tysabri", or "would it help to talk to? ... (to enable a person to get this med cheaper)", etc.

Regardless of whether I've tried it this med or not, I know a lot about this drug, and even more about this disease . . . and my answers on this forum are always meant as supportive or informative, at least to the "larger audience".

I have occasionally posted a few links to new information there, and/or links to other threads that have started to "discuss" new information. "Who" posts that information is totally irrelevant, UNLESS they add on a "speculation" that has the effect of misleading people . . . in which case I DO jump on and say something. I hope people would correct me when I am wrong too.

I have no problem answering to your double dare (I'd even be willing to bet you a $buck$ on that one ;)), but it's a two way street, Sally.

Cherie

I'm joining this conversation late! A lot going on in my life right now. I want to go back to what marckstck posted. I found what those neuros doing very interesting!

On one hand, I'm glad they are being pro-active, and doing some research that could benefit all of us on Ty.

On the other hand, if they came out and said it would be best for all Ty users to have a spinal every 6 months, I might decline!

That is an expensive and invasive test that may or may not be helpful. I'm going to have to think on that over the holidays.

Definitely invasive... however, what is the cost for the spinal tap to be performed? It was covered by medicare for me in Canada (and done during diagnosis), so at this time I don't imagine a second would be done.

They'd have to have me 100% convinced that they were looking for something other than related to MS before I'd undergo another one. :eek: One week in the Brain Trauma Unit was enough for me! :(

Cherie

I went back and looked at my spinal in 2006. It was a little over $1200 for the hospital, and another $500 for the doctor.

I didn't have any troubles with it. In fact, after it was over, I felt better than I had for months. My husband teased that maybe I needed one more often to relief the pressure of my massive brain of knowledge!

Eep. That cost is nuts though. :eek:

I'd definitely refuse if medicare wasn't covering the cost, beyond my initial LP I had done (and as Cherie remembers, it was rather silly they went ahead and did that LP to begin with). :rolleyes:

I suspect Marc's doctor is doing these because he is "studying" if there are early markers for PML, not just because he is "monitoring" his patients. In that case, people who have agreed to this procedure are doing it for the benefit of science, not to preempt further damage.

If I were taking Tysabri, and there was evidence that I may have developed PML, I guess I'd have to agree to a LP. :D In fact, I doubt very much that anyone currently on Tysabri would have a choice in the matter . . . IF they are suspected of PML and removing the person from the drug (+plasma) didn't effectively alter their course.

Cherie

Oh yeah I'm with you for searching for PML, but for an MS diagnosis second opinion (for example), no way in heck would I allow them to LP again. :eek:

I had enough to be diagnosed initially WITHOUT that LP :p

Cherie,

If you really knew about Tysabri, you would know that it is twice as effective as our other choices. The unknown is the long term safety of using the drug (I'm at two years as of Monday, 22 Dec no problems to report) regarding PML and other opportunistic infections. The other unknown is the outcome of PML. It was assummed that the outcome would be death or severe disability. 3 of the 4 PML cases since relaunch of the drug under monitoring have resolutions. 1 of the 3 patients has died - cause of death is unknown but PML or IRIS from PML treatment is suspected. The other 2 patients are out of PML danger. One only had minor weakness.

While it is always good to have a balanced discussion, your assessment of risk/reward comes from your individual situation of MS risk in using a less efficacious MS treatment.

Chris

Merry Xmas to you too, komokazi. :)

I suspect that I know much more than you give me credit for ;), but today is not a good day for debates for me. I have turkey to cook, kids to entertain . . . and it is Xmas day around these parts. :p

I will have to come back to your points in a day or so.

Thanks for your input.

Cherie

Merry Christmas back at you Lady Express
 

Cherie,

Definitely enjoy your day with the kids .... cooking not so much. I just wanted to post that I take Tysabri because of it's effectiveness - convenience and lack of side-effects for me are just bonuses. For me, the Tysabri risk/reward choice was easy - On rebif I was in a glider slowly/constantly losing altitude (slowly but still losing altitude) while also enduring the mental strain of fighting the flu like side effects for 4 days every week for week after week, month after month. I felt going into Tysabri that the risk of PML would ultimately be less than 1 in 1000 and that PML would not ultimately have to be fatal as I would treat any relapse like event as potential PML and stop taking the drug. I look forward to your comments.

Chris

Hi Chris,

This discussion was about the announced 7th case of PML, and the recent death that occurred. It was not intended to center around how effective Tysabri is, or whether some might think it is a risk worth taking ... so that’s why you didn’t run into many comments regarding those points in this thread.

As far as efficacy, although Tysabri claims to be twice as effective in reducing relapses, there has never been a head-to-head trial against the CRABs. It is really impossible to know if it is "more" effective, as results from these trials may be very skewed by any number of factors:

http://www.ncbi.nlm.nih.gov/pubmed/18437041

http://www.ncbi.nlm.nih.gov/pubmed/1...t=AbstractPlus

Tysabri claims to be about twice as effective in reducing relapses, however, IMHO, relapse rates aren’t a significant measurement of “efficacy” with this disease anyway. Even if Tysabri proved twice as effective in reducing relapses in a head-to-head trial, unfortunately that does not mean we are going to be any less disabled in the long-run.

While reducing relapses might be pleasurable, Tysabri proved to be only slightly more effective (in absolute terms) then the CRABs for short-term disease progression. There is no long-term efficacy measure of this drug for disease progression yet, so that is another “unknown” that people need to measure up against the risk, obviously.

http://www.neurology.org/cgi/content...916.38629.43v1

I am glad you are at two years with no problems to report, but that doesn’t mean there haven’t been any with others.

I agree that “the unknown is the long term safety of the using the drug regarding PML and other opportunistic infections”.

However, I disagree that:
- “the unknown is the outcome of PML”
- it was necessarily “assumed that the outcome would be death or severe disability”
- “3 of the 4 PML cases since relaunch of the drug under monitoring have resolutions”

We knew/know the current “potential” outcome of PML, at least at this moment in history. We know that people may die from PML ... since two out of three in the original trials did. We also know that even IF they initially seem to survive the PML (as the recent US patient did), they may succumb in weeks, months, or die from IRIS (used to treat the PML). We don’t have autopsy confirmation on the recent death, but I'm “speculating” that Biogen spokesperson would not be “announcing” her death in the same breath as the fact that she got PML from Tysabri . . . if her death was unlikely to be related to the drug.

We also know/knew patients might live through PML. . . since the third trial patient in the trials did, as have 3 people since. We don’t know precisely “how” disabled that ANY eventually became from PML as much of the details are deemed “patient confidential”. In fact, it was only a few weeks ago that we got “news” that the Florida woman who got PML in Oct, was home and “recovering” under her doctor’s care. Next we know, she’s died.

So, it’s probably going to take time, and perhaps even a court case before we ever find out EXACTLY how disabled ANY of the people who got PML have become, or what the long-term prognosis might be for them.

I don’t know what that sentence means . . . ?

As I said previously on this thread, Tysabri “is at least as effective as our other options, it is much more convenient, and there are less general side-effects.” I get why some people want to use it, and that they may be willing to take a risk . . . just as you would likely understand how others feel the opposite.

Well, you were more wrong then right. . . at least so far. That is the reason we still talk about the risk though, as like you, some people did go on it thinking the risk would be much less then was predicted.

Currently the risk for PML is at about 1:1357, so we are not that far off. While there are many thousands of people on it now, the risk they estimated was 1:1000 for those who’ve been on it for 18+ months. Currently there are 9500 that have been on that long, or longer, and 7 cases of PML . . . so there estimation was pretty close ... SO FAR.

Cherie

:Good-Post:

As always, very thorough Cherie, and you addressed a few of the points that I too had questions about.

Interesting read thus far :)

Agree to disagree
 

Statistically it would be impossible for confounding factors to have caused the difference in relapse rate. The Tysabri trials had almost 2000 patients which would eliminate any small sample bias. You also conveniently ignore the 6% of Tysabri patients who developed persistent antibodies to the drug effectively rendering the drug ineffective for them. These patients pulled down the reported effectiveness of the drug.



I would hardly use the word "pleasurable" to describe the need to avoid relapses but then again I'm not into inflicting pain on myself and I don't live in a parallel universe. Nothing about this disease is pleasurable.



The 3 original PML cases in the trials and their outcomes can hardly be considered representative since these cases occurred in an environment where PML wasn't even being looked for and these cases were mistreated by applying even more immunnosuppression. In short, they didn't have a chance. In the commercial setting, Doctors are monitoring for PML and removing Tysabri from the bloodstream if detected. Significantly different situations to draw an apples to apples comparison.





Be careful in quoting PML risk rates without all the correct numbers. We know that there have been 4 PML cases, 1 at 14 months, 1 at 14 months, 1 at 17 months and 1 at 26 months. The first 14 month and 17 month cases occurred prior to Sep 31, 2008 where there were 18,000 patients at 1 year, 9500 at 18 months, and 4000 at 2 years of treatment. The next case occurred on Oct 31st, so the number of patients had increased (probably by 1500 per month in each category). The next case occurred on Dec 15th so add another 3000 in each category (2 months of patient treatment). The denominator has definitely increased and I believe you are using the wrong numerator. Including the 3 PML trial cases with the commercial setting cases is apples and oranges as the commercial prescribing restrictions are obviously significantly different from the clinical trial use. The other confounding item is that only 1 PML case has been confirmed under the US TOUCH program with the other 3 PML cases occurring in Europe which doesn't have TOUCH restrictions while the number of Tysabri patients was higher in the US than in Europe. Does TOUCH offer further PML reduction?


Cherie, at the end of the day we're going to disagree on the relative benefits and risks of the drug that I have chosen probably because you've made a different treatment decision. I certainly respect people making different choices for their different circumstances and the last thing I would ever do is try to "sell" someone that my choice was correct or downplay some other choice as being incorrect. That's the line we all have to walk, being informative without our predisposed biases to the choices we have made.



Chris

Let's agree to disagree
 

Cherie,

Before I post retorts to your writings, let me first state that we have both made the treatment decisions we have based on our assessments of the data available and our individual cases of MS. The point of these discussions is to share information to help others in their treatment decisions without the bias we have due to the treatment decisions we've made.

It would be statistically impossible for the Tysabri effectiveness results to be due to confounding factors. The Tysabri trials had almost 2000 patients which would eliminate and small sample bias and there was a Tysabri/Avonex comparison versus Avonex alone arm. The other factor you choose to ignore is that 6% of Tysabri patients developed neutralizing antibodies making the drug ineffective for them. 6% of the TYsabri patients were effectively on placebo and the drug still reduced relapses by 70% relative to placebo.

Avoiding relapses is "pleasurable"? *edit* Avoiding relapses is necessary maybe not sufficient but definitely necessary. Besides nothing about this disease is pleasurable.

Using the PML outcomes from the trials to paint PML outcome expectations is flawed since in the trials, PML wasn't being looked for and was mistreated by adding further immunnosuppression. These patients never had a chance. In the commercial setting, Doctors are watching for PML and trying to remove the immune supression when detected. It certainly doesn't mean that PML won't always remain a serious infection but it does mean that the outcomes won't necessarily be the same.

Please don't quote PML risk numbers that are incorrect. You scare uninformed patients taking the drug and scare away others that are evaluating their treatment decisions. The 3 cases of PML that occurred in the trials don't belong in the PML numerator as we are trying to assess PML incidence in the commercial setting with the commercial restrictions. So we've got 4 PML cases for the numerator. Your patient numbers in the denominator are also incorrect as they are as of Sep 31, 2008. In the 3 months since then more patients (probably 1300 per month) have reached the 1 year, 18 month, 2 years and over treatment threshold. The other confounding items in making this calculation is that 3 of the PML cases occurred between 14 and 17 months and one at 26 months and that only 1 of the cases occurred in the US TOUCH program even though 60% of the patients on the drug are in the US. Do you use the 1 year patient numbers or the 18 month patient numbers given the 14 month cases? Does the TOUCH program provide further PML risk reduction through tighter patient admittance criteria and clooser monitoring? There are a great deal of unanswered questions and certainly a great deal of discussion needed above and beyond a dismissive comment that I'm wrong and the risk is about what the label says.

Chris

Hi again Chris,

*edited*

- we have previously had this conversation about stats & efficacy *edited*, and there are some people here who can become very upset by the re-hashing of this subject :eek:

- you don’t need to worry about ME being biased towards any treatment option, as I have had MS for 18+ years and have never even been on any DMD. Either way, it’s not a competition, at least from a patient perspective.

However, since you are missing some of the information you need to make an informed argument, I will provide a very quick synopsis on the numbers . . .

The risk profile of 1:1000 is based on all of the people in the original Tysabri trials, not just those in the MS trials. This included the Crohn’s patients, and it was determined that the risk for PML was 3:3000 (or 1:1000) for those on a mean of 17.9 (18) months.

No matter what other drugs the patients were (or had been) on in the trials, the best go-forward projection Biogen could predict (for PML potential”, while on monotherapy), was 1:1000, over 18+ months. You, and everyone else who’ve been on it, accepted that risk ratio.

Regardless of how you (or I) calculate the current ratio of cases, the stat is lower then was predicted. How could anything that I say (which is still less than Biogen’s prediction of 1:1000) be “scaring” anyone?!? :cool:

Virtually all PwMS are all immune compromised, and/or have used prior immuno-modulatory/suppressant drugs. Some suggested that the cases in the trials might have only occurred because of the immunosuppressant qualities of Avonex and Tysabri combined . . . but we now know that people even on monotherapy, i.e. only ONE drug at a time, might be too immune compromised to safely start on Tysabri.

The prescribing criteria for Tysabri states that it is “... recommended for those who have not been helped enough by, or can not tolerate another treatment for MS ...”. That basically ensures that most of us have PREVIOUSLY been on “some” drug that has affected our immune system . . . and would “justify” every case of PML to date. Well all, except one... the European patient who had used NO treatments previously.

The bottom line is that we now know that PML is just going to happen occasionally with Tysabri anyway . . .

TOUCH is in place in the US, to screen out “the most” at risk patients ~ those patients who have used/are using meds that might increase their odds of getting PML. If TOUCH protected people from PML, the Florida patient wouldn’t have gotten it.

Our neuro’s don’t want us to die any more than the makers of Tysabri do. They are making their best judgment call, in the US and in every country that Tysabri is available . . . so your point about “where” people lived when they got the PML is irrelevant. Careful selection and intricate monitoring of patients helps, but it will obviously not stop PML from occurring.

As for the current stat, we can’t count all 35,500 people who’ve been on Tysabri, some who’ve been on for as few as ONE or TWO infusions. While my calculation for a ratio wouldn't be 100% correct, it is as close as we can get and definitely much more accurate then “only four cases of the 35-odd thousand that are on it . . .”.

The 9500 number confirmed in Dec/08 (those who’ve experienced T for 18+ months) includes those 3000 patients who used Tysabri during the trials. Since it seems to take 1 – 3 months to confirm PML, I really don’t think it is necessary to “speculate” how many more (or less) people might be on Tysabri since the last confirmed count.

Nor do we know how many are currently being investigated for PML since the 9500 was confirmed.

If you prefer to take out three patients that got PML in the trials, you will also have to reduce the number from 9500 (- 3000, that were in the trials) to 6500. That would still result in a current “experience” ratio, as best as we can calculate it, of 4:6500 (or 1:1625). . . . which is not THAT far off 1:1357.

There were hundreds of drop-outs in the trials, as there are some % in any trial. Generally those people dropped out because they got too sick (or otherwise didn’t respond well to the treatment during the trials). They are NOT COUNTED in the final statistical analysis for efficacy, so the stats we hear about are based on those who thrived (reasonably well) throughout the duration.

I already spoke to the efficacy comparison between our various drug options, and attached a few links to make my point. And, while it is nice not to have relapses, I (personally) am not going to risk my life to try to avoid them . . . even with the odds as LOW as they currently are.

If you are more comfortable quoting whatever numbers you feel ok with, that is entirely up to you. I will stick (and answer) to the numbers I believe are correct. If reality (from someone else’s perspective, that apparently you don’t agree with anyway) “scares” you . . . perhaps you shouldn’t be have taken the risk associated to this med . . .?

I wish you (and everyone else) well, Chris. I really do hope the odds for getting PML from Tysabri ultimately pan out to be MUCH lower then anticipated, and that Tysabri proves to be a relatively safe (liver function, cancer risk, etc....) and effective treatment option for this disease in the long-run.

Good luck,

Cherie

Wow, I can't know anything since I'm new
 

*edit* You were the one making statements about Tysabri being only about convenience which I believe I appropriately replied to. *edit*

Your PML stats are still wrong even though you continue to take every opportunity to re and repeat them.

*edit*

It shows BiogenIdec data of number of patients on therapy (commercial and clinical) on various dates in 2007. Note that there were 0 (zero) patients at 1 year of therapy until Dec 2007 - The previous trial experience is not quoted in the reported number then or as of Sep 2008. When they say trials they are talking about the active trials they have ongoing. And the 9500 is as of Sep 2008 - they won't update it until they report 4th quarter earnings.

I'm hardly scared by your numbers as I know with certainty that they're wrong. I'm thinking of others who may look at your postings and take them as gospel.

stats
 

Your PML stats are wrong. Check page 14 of this link:

//library.corporate-ir.net/library/14/148/148682/items/278364/Q4-07%20Earnings%20Slides.pdf

The safety information lists 0 (zero) patients at 1 year of therapy until Dec 2007. The reference to trials does not include the trials for approval but the trials that were started upon Tysabri reintroduction.

You are also misinformed about the us TOUCH program. Part of the program is the screening for putting the proper patients on the drug. The more important part is the monthly pre-infusion checklist to monitor for any new or worsening symptoms. Let's see PML in 1 out of 19500 Tysabri patients in the US (with TOUCH) while there's been PML in 3 out of 16000 Tysabri patients in Europe. Seems like TOUCH could be making a difference.

Clearly you think you know and are correct about everything regarding Tysabri so there isn't much point in discussing this further.

Chris

ok

I have had to do some edits here and need to respectfully request that the guidelines be heeded

http://neurotalk.psychcentral.com/showthread.php?t=1293

perhaps you should both just agree to disagree and let it go, if you cant disagree agreeably:rolleyes:

if the back and forth continues in this confrontational way I will need to close this thread

thanks

This is just more for my understanding of where both of you sit, as far as your MS. I've had my disagreements with Cherie before, and maybe I'd be better about her stats if I knew her situation better.

And Chris, maybe you could address this also, so I understand where you come from.

I'll start with me. First symptom I can firmly state with MS was Feb. 2002. Wasn't dx'd until 2006. I was on Avonex a year (2006-2007), had more and enhanced lesions on first follow-up MRI, so went on Rebif for a year(2007-2008). No new lesions on 2nd MRI (I have them every year about March), so Rebif holding things at bay, but I was having trouble with itchiness and general fatigue. Started Ty in April 2008. Other than a half hour of chills after the infusion, rest of the time I'm super! Will have an MRI in March to see how those lesions look after a year on Ty.

I work full-time. I have a tingly left hand, get tired easily, bouts of vertigo off and on, but nothing that a little rest doesn't fix. I'm very busy, and manage to do most everything asked of me. I've learned to let little things go, but if I need to work hard, I can pace myself and get it done over time.

So now, Chris and Cherie, what DMDs have you been on/or not and why, do you work full-time, what kind of disability do you have, etc. Cherie, I know you smoked in the past, but I don't know if that is true now. Maybe the smoking helps MS???

Do you have MRIs yearly, or every two years. I know Cherie says she's had MS for 18 years. Does that mean you were dx'd 18 years ago?

Answer to your question
 

I've been diagnosed for 6 years know. Started with Avonex for a few months and then my Neuro switched me to Rebif. Endured the the flu like side effects for 3 years. My MS was relatively stable (maybe 1 relapse) but I felt like I was in a glider slowly loosing altitude. The continual flu like side effects wore on me mentally. Switched to Tysabri in Jan 2007. I've felt a lot better - less fatigued, more responsive legs, less spasticity. Heat doesn't bother me as much. Not back to running marathons but definitely not in the glider anymore.

I've got some disability with my legs - I walk unaided but definitely labored/not fluently and I have falls infrequently when my legs get stuck on lip, ledges, themselves.


I work part-time since I have a great employer that allows me to work 20+ hours a week and still maintain my health benefits. Helps that I'm an engineer and have a desk job.

Chris