Tysabri - 9th case of PML
 

The 9th case of confirmed PML (or 6th, Post-marketing), was revealed on the Biogen site on Friday . . . .

http://arthritis.about.com/gi/dynami...e%2F019_2.html

So that brings the total ratio of confirmed cases (for those who've used it for 18+ mo, including trial patients), to 9:24,400:

14,400 – used it for 18 mo (post-marketing)
6,800 – used it for 24 mo (post-marketing)
1,800 – were on 18 mo (during trials)
1,400 – were on 24 mo (during trials)
24,400

Or a current ratio of 1:2711.

Cherie

Please stop mixing apples and oranges by including the original trial data with the post marketing experience. Patients deserve honest information about their potential risks. 6 PML cases in the post marketing setting with almost 25,000 at 12 months or greater and 14,400 at 18 months as of the end of Mar 31, 2009. It is also important to note that 4 of the 6 PML cases appear to be in German patients which begs the question of whether the German usage of Tysabri is outside the US TOUCH procedures. I'll leave the calculation of the PML risk to the biostatisticians.

Personally, I really don't think it makes any difference to the number of PML cases as whether it happened during the trials or afterwards. The bottom line is that the patient being treated with Tysabri ended up getting PML and that IS the concern.

I also don't think that it makes any difference that the German cases happened outside the Touch program. The German medical system, the last time I heard, was excellent. I read on another MS forum that the German's were being very honest when it came to reporting problems with Tysabri use.

I fear that the PML count for Tysabri users will continue to climb and make the MS patient's decision to try the drug even harder to make.

Harry

I am pretty sure that all Ty users including those from the trials is approx 52,000. So using this number with total pml cases would make the odds a little less than 1/5800. The number post trial is appox 40,000 Ty users with 6 pml cases making these odds around 1/6700. My mind just can't remember where I read the numbers on Ty. I hate when this happens and I just read it recently...sorry:o
Linda

That's sad for those who passed however the odds are too great. Every drug we take can have bad side effects. For the good I have seen Tysabri do I say the risks are too small to not give it a try. Olhipie was on it for 7 months in 2007. Actually made him sick after each dose. :(

Calculate it however you choose, Chris . . . the numbers are all there, so if reducing it by three (or taking out the German cases) makes YOU feel better, go ahead. Whatever floats your boat. :rolleyes:

The original risk ratio of 1:1000 was calculated on the basis of how many had used it for 18+ months. They calculated the mean amount of time that everyone in the trials had been on it, and there were 3 cases of PML, so that gave a ratio of 3:3000, or 1:1000.

We don't have a 'mean' of 18 months on the market yet, so the best numbers we can use for comparison is how many have simply been on for 18+ months. I provided those numbers, which is 24,400 people with 9 cases of PML to date, or 1:2711.

Cherie

ummmmmm

careful with the tone of these responses please

"apples and oranges" and "deserve honest information" and "whatever floats your boat" are bordering flaming each other and not conducive to an intelligent discussion of the topic, but reduce it to a spat.

if you must disagree, please do so agreeably

we really dont want to have to intervene here but if the guidelines are broken we have to

thanks

[QUOTE=lady_express_44;498927]Calculate it however you choose, Chris . . . the numbers are all there, so if reducing it by three (or taking out the German cases) makes YOU feel better, go ahead. Whatever floats your boat. :rolleyes:


The apples and oranges comparison is easily supportable. In the original trials ,which drove the 1:1000 label (3 pml cases:3000 patients), the PML cases occurred in patients who were on other immunosuppressants (Avonex/1 recently had Remicade and Imuran). In the post-marketing setting, concommittant immunnosuppressants are specifically contraindicated i.e. shouldn't be being given. Different usages (apples vs oranges) can clearly affect the relative risks of an opportunistic infection.

In no way do I exclude the 4 PML cases from the 6 post-marketing cases confirmed. It does suggest given the patient numbers in the US and other countries excluding Germany and only 2 confirmed cases versus the patient numbers in Germany and the 4 confirmed cases that this isn't just random chance and normal distribution. I don't know how the Germans are using this drug compared to US Touch (although the husband of PML patient #5 postmarketing said that Germany had no periodic MRI monitoring) but I would certainly investigate to see if there are any identifiable differences that may explain this.

All I know is that those numbers don't mean squat to most of us...my eyes cross when I see ratios, etc. I truly get brain fog...
What the discussion needs, as far as I'm concerned, is how those who are on Ty feel about the risk/benefit ratio...
I have talked to a few people who are on Ty, and they feel it's worth the risk...they feel so much better as far as their quality of life is concerned. So many of us on DMDs have side effects or do not get relief from our sxs.

If a patient feels that the quality of life is worth the risk, and is fully informed, then that is the barometer I wish to go by.

While I have no doubt that Germany's medical system is good, the husband of PML patient #5 (post marketing in Germany) just posted that Germany just instituted periodic MRI monitoring for Tysabri patients in response to the first 2 PML cases. All systems clearly have their weaknesses.

Chris

EACH of the PML cases has it’s own individual “story”, and I'm really not interested in re-hashing each case with you again.

I think it suffices to say that some were on Avonex, some had/were treated with steroids, and yet others were only ever previously on DMD’s or NOTHING before starting Tysabri. Some come from America, others are from the UK. Some lived & some died. All very sad.

All 9 got PML, and they wouldn’t have gotten it without Tysabri.

Fully informed means understanding the risks . . . at least it does in my opinion. :confused:

This information is NOT posted for the benefit of those who've already decided 1:1000 is a comfortable risk ratio. It is an update for those who HAVEN'T yet decided.

Cherie

What's sad is what MS does to people physically and mentally and the corresponding impacts on family and friends.

Sorry, but the PML cases do have to be looked at at least in groups - PML risk and outcomes in the trial where they were using other immunnosuppressants/weren't looking for it/treating it and PML risk and outcomes in commercial use where they are using it in monotherapy/they're looking for PML and trying to treat it.

As I've said before risk is a function of chances of occurring and outcome of occurrence. If your concern is to fully inform patients considering Tysabri please give them the full and accurate information.

Tysabri scares the crap outta me! I dont believe I would ever consent to be on it. Just way too scary for me. I think those that do chose it are incredibly brave, and have boat loads more courage than I could ever muster. I think it has much much more to prove before I would even think about it. But thats just me.

Stay tuned. Biogen and Elan are working on new ways of detecting PML earlier and identifying those most at risk.

Dejibo - I am so in awe of them too!! I thought I was tougher but fear of discomfort and possibles showed I'm not. All you brave people - hats off. redpenguins re-doing with hy-cy is braveness to me. I'm hoping stem cell will helps me as a PPMS. It's hard to have nothing to try.

Nothing seems to be targeted for PPMSers to use. I guess being a minority in the MS world make us financially not a possible concern to big pharmiceuticals. Clinical trials for PP are rare.

I've been told that there are actually more considerations than finance with PPMS trials. They really understand it so much less which is scary considering how little they understand about RRMS. The damage is harder to monitor on MRI than RRMS, so they can't determine success by affecting lesion load. They also can't look at a reduction in relapse rate to measure success. It just makes it very hard to design a research study that can get funded. Am I making sense?? I know what I'm trying to say, but getting it from the brain to the keyboard isn't easy today.

My lesions are very atypical for RRMS, but look more like PPMS, however I have obvious relapses and remissions. I respond well to IVSM unlike most people with PPMS, so I am a mystery. My neuro doesn't want to label me PPMS because I don't fit that, but my lesions don't fit the other, so he calls me atypical MS. He honestly does not think that ANY of the current approved DMD's would help me at all, just like they don't help PPMS. It's such a weird disease with strange manifestations.

If he told me tomorrow that he thought Tysabri would work for me, I don't honestly know what I would do. I have several friends who are on it, but I don't know whether I would be so brave. I can see that the odds are actually improving over time from what they originally published, but I think I would like a couple more digits on the one side of that ratio. :eek:

A drug like Tysabri has a way of truly finding not just the weakness in a country's medical system but in pointing out the various ways the docs and infusion clinics handle the patients. Some of the stories written by these patients on the net really show what the varied level of care is with this medication.

And now Biogen and Elan are spending millions of dollars on new ways of detecting PML! To say that they were not looking for PML or similar conditions during the trials is simply not correct. Biogen was warned repeatedly by Dr. L. Steinman (one of Tysabr's founders) that these conditions were very probable and likely to occur. So what did they do?....push for approval after one year of Phase III trials which of course got them into a real mess!

You have to understand what Biogen and Elan are all about in the world of big pharma and IT'S NOT about the health of MS patients. It's about the bottom line and getting as much profit as they can.

Tysabri is an immensely expensive drug to use and the follow up costs with patient monitoring and MRI's is making it beyond expensive. The efficacy has been similar to other MS drugs....some do very well on it, others more or less remain the same and some become very sick and have to stop it altogether. I guess time will tell if it was worth it.

Harry

Harry,

God bless you but I have to disagree with you. I thank God for Tysabri because I feel so good since being on it.

I'm thankful that it's available in the US and that we have good health insurance (though very expensive) and I can have the infusions.

I'm also glad they're looking for better ways to detect PML. I don't know what more they can be doing. They're keeping an awesome drug on the market IMO for those who need it, and taking steps to avoid the worst of all side effects (PML).

We need naysayers to keep things in balance so I don't fault you or Cherie or others for questioning Tysabri or other drugs. Matter of fact, I used to be in agreement with you. But now that I've been on Tysabri for almost two years, I have to agree with those who were singing its praises for so long since I feel so much better and my life has improved.

Harry,

I'd highly encourage you to look at the abstracts being presented at the AAN 2009 Meeting next week. There will be a lot of data presented on patients pre and post Tysabri (Relapse rate, EDSS, QOL measures) that may alter your efficacy perception relative to the CRABs. You might also want to recheck your info on CRAB costs as their prices hacve crept up to within 10 to 15 of Tysabri's costs.

Chris

Wiz, I am of two minds, to be honest. The important thing to me is that people feel good, AND that they are safe.

Once all the kinks are worked out of Tysabri, and I really hope they are one day, I might very well try it myself.

For now, there are some 40,000 people on it, and many millions not yet willing to try it. I am just one of them, and I don't mind saying why I won't.

Cherie

Hi Wiz,

My concern isn't with Tysabri because the drug is obviously helping a number of people...and you can certainly atest to that!!

It is with Biogen's handling of the drug from day one and the incredible rush they did to get it into the MS market. In my opinion, that was driven by pure greed because of the huge $$$ potential they saw after year one of the Phase III trials. They went so far as to partly publish their marketing plan on the internet, stating the hundreds of thousands of MS patients they expected to use the drug as well as the millions and millions of revenue they were going to get. They figured that within 18 months of its approval, they would recover all of their development costs.

They took this course despite numerous warnings from other researchers about the potential problems that Tysabri could cause. We saw their top execs makes millions in stock option profits before the drug was pulled and then they raised the cost of the drug about 20% before it was re-released...so it was the MS patient/insurance companies who were made to pay for their mistakes.

Again, that's what irks me about them. I wish you continued success with the Tysabri infusions and hopefully you remain healthier than in the past.

Harry

Chris,

I am used to seeing the abstracts for MS medications over the years...for the past 40+ years in fact. And yes, those being presented for Tysabri at the AAN 2009 meeting will look very nice...they always do.

My comment about Tysabri's relativity to the CRABs has to do with the generalities of patients improving, staying the same or becoming worse. Not in the actual comparison numbers because the CRAB numbers are really quite lousy and it doesn't take much to better them significantly. Tysabri's breakdown in these three groupings will be the same because of the huge different effect medications have always had on MS patients.

And to comment on the price increase of the CRABs....pretty disgusting!! Here are drugs that got orphan drug status (with the exception of Rebif if I can remember correctly) from the FDA and have been around for about 15 years....yet their price continues to go up only because of the huge cost of Tysabri. But their advantage, if you can call it that, is they don't have the ludicrous infusion costs that go along with Tysabri.

I'm afraid, Chris, the MS patients of the world are being taken advantage of by these companies whose sole motivation is adding to the bottom line. Now there is nothing wrong with trying to improve your profits to the highest level but when you follow how these companies have done that with these drugs, it makes me shake my head!!

Take care.

Harry

I don't think you can blame Biogen for high infusion center costs. My last couple of doses of Ty were around $2650 for the med, and $150 for the infusion center. I don't think my Rebif or Avonex was much cheaper than that for the med. I'm on Copaxone now, and I don't know what the total is, just my co-pay.

I'll tell you what is heart-breaking. When you go on Ty, love being on Ty, then develop NABs and have to go off Ty and move to Copaxone. PML was never a concern. If you get it, you get it. I could also be hit by a car, but that isn't going to stop me from driving.

Random thoughts from an unhappy C user!

While Biogen doesn't control the costs of the infusion centers, the very nature of Tysabri and its related problems have certainly thrown caution to the wind for these centers. And when there is possible high medical liability problems involved, up go the costs! The CRABs, in general, are about 25 - 30% cheaper but injecting yourself often and the heavy side effects for many users, make them more difficult to administer.

Sorry to hear that you ended up with NABs while trying Ty. Because of its potency, that is one of many problems with it. And while PML was never a concern for you, it is likely keeping thousands and thousands of MS patients from trying it.

Harry