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.

Cherie

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... ... 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?

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..

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