FDA reporton Tysabri

[D Bergy]

Here is the latest report concerning Tysabri from the FDA.


Audience: Neurological healthcare professionals, patients

[Posted 09/17/2009] FDA continues to receive reports of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri. Tysabri was approved by the FDA for the treatment of relapsing forms of multiple sclerosis (MS) in November 2004 and for moderately to severely active Crohn’s disease in January 2008. From July 2006, (when Tysabri marketing resumed) to September 8, 2009, 13 reported cases of Tysabri-related PML were confirmed worldwide in patients being treated for MS with Tysabri monotherapy. There have been no postmarketing reports of PML in patients treated with Tysabri for Crohn’s disease. Less than 2% of Tysabri use in the U.S. has been in patients with Crohn's disease. Based on available data from the U.S. and outside of the U.S., the current rate of PML in patients who have received at least 24 infusions ranges from 0.4 to 1.3 per 1,000 patients.

The risk for developing PML appears to increase with the number of Tysabri infusions received. At this time, the FDA is not requiring changes regarding PML to the Tysabri prescribing information or to the Tysabri risk management plan, called the TOUCH Prescribing Program.

Read the MedWatch safety summary, including a link to the "Information for Healthcare Professionals" page, at:

http://www.fda.gov/Safety/MedWatch/...tyAlertsforHumanMedicalProducts/ucm182667.htm



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[BWS1982]

Not to be pessimistic (I'm really trying to just be realistic and cautious) but I suspect the potentiality for PML in Crohn's patients is perhaps the same as the MS patients, it's just that the ~ <2% rate of purpose/usage is mitigating the reports of Crohn's incidence...just maybe? The math says if 1 (or less) part per 50 is taking it for Crohn's, and 13 have gotten PML/died, you have to assume that, statistically, there won't be a PML case in Crohn's patients until the PML cases in MS patients has reached 50 (or more, as it said "less than 2%")...that's just simple math. Nothing more than basic ratio calculations.

Also, the risk is down with monotherapy, but immuno-suppression is very prevalent in Crohn's treatment, making it a big shift to go to just Tysabri, so as to reduce the risk. But how long does the body have to be off all other meds to safely assume the immune system is back to regular status? 6 months? 3? If you take Tysabri too soon, the risk with Crohn's patients may indeed be higher, even in monotherapy, because I'm not sure if there's a factual and totally flawless time frame assigned between going off immunosuppressors, and starting monotherapy Tysabri. I doubt they can say without a doubt they know that time frame, it would have to be conjecture and estimation, though they can wait a VERY long time and probably safely assume it's all clear to start "monotherapy".

I honestly can't speak on any other factor that would attribute to the contrast in reported PML when comparing the two applications, IBD and MS, and for just 13 cases, it's hard to come up with any rationale, because back last year, I was told just 4 had died. I think the risk should be the same, Crohn's or MS treatment (w/ monotherapy), and the real variable is the monitoring and good medical care, TOUCH, etc...

 

[D Bergy]

The numbers of Crohn's patients using Tysabri is so low that an accurate statistic is probably not really possible, since large numbers are needed to draw any conclusions.

MS is probably a pathogen driven disease that can result in autoimmune problems from the pathogen. Similar to chronic Lyme disease, as opposed to Crohn's which is likely a hereditary autoimmune component coupled with later pathogen exposure, that produces symptoms.

This hypothesis is not written in stone either, but it is the probable causes from the information I have gathered on the subjects. A person can hardly avoid learning about MS when investigating Lyme Disease, since so many similarities exist between the two. They are often misdiagnosed because of the similarities.

The bottom line is that the diseases have some common characteristics, but the mechanisms are different enough that the results of one group using Tysabri would not necessarily translate into the same results for the other.

Just idle speculation, but larger number of Crohn's users would be needed to actually know the likelihood of adverse affects to that subset of users.

Dan

 

[saidinstouch]

There was a report recently that basically every person on tysabri has an increase in the JC virus which normally resides in the kidneys of 90-95% of the population. They aren't actually sure why PML develops given this result so there is clearly another factor that leads JC to become PML rather than just an increase in the viral load. The one benefit to crohns patients is that we have typically few if any neurological symptoms so it is fairly obvious when there is a problem and can be reversed. As to the question of how long things like pred suppress our immune system, I am no expert, but based on my studies I would say the suppression reverses within a few days of the drug being cleared from our system due to the nature of the effects. For something like remicade or humira, it would likely be a month or two for it to be fully cleared since the dosing schedule is often based on keeping loads of the antibody at therapeutic levels and the dosing is 2weeks-2months typically so figure somewhere in that range. Once the antibody is cleared, the system functions again quickly in most cases.

 

[BWS1982]

The numbers of Crohn's patients using Tysabri is so low that an accurate statistic is probably not really possible, since large numbers are needed to draw any conclusions.

I would again have to side with this synopsis. What I'm saying is we have ratios/proportions of about 1 out of 50 patients using Tysabri for Crohn's (49 for MS), so we'd need roughly 50 cases of PML to see equal distribution in the correlating patients, ie: just one case of PML in a Crohn's case per 49 of MS cases...that's the inherent math that dictates my assumption based off historical data.

Though I'm a bit confused because the report said none of the PML's were Crohn's patients, and Shantel's conference stated there's been one, so there's a discrepancy somewhere.

The good thing is as you noted Shantel, that the likelihood of PML within the first few months shows to be greatly down (as it's been basically nonexistent thus far) and that's a great headway on getting to learn about the effects it'll have on a potential patient. Take them off it if it's not going to do anything.

To finally add, I'm well aware of the risk benefit ratio and the minute fraction of PML out of thousands on Tysabri, (same as the lymphoma on my Immuran meds)... my brother's MIL is on it for MS and says it's done wonders. Here's my thing: I got screwed on the "statistics" card and drew a short straw out of thousands of long ones. How? I have Crohn's Disease, out of all the healthy people wolfing down bad food and living with sin and vices, I, a health nut, get a 'digestive/immunity illness'...I put little faith in the "statistics" of something and take each risk with a grain of salt. That includes car accidents, cancer, the works. The whole "it'd NEVER happen to me" went down the toilet with my bloody diarrhea, anyone can get a bad hand, and I'm more cautious for it now.

 

[D Bergy]

Thanks for setting the record straight Mike.

This is the kind of report that can lead you to the wrong conclusion when you do not have the whole story.

It would have been nice if they included that information in the FDA report.

I guess the theory that it is the combination of drugs that causes problems, has a great big hole in it right now.

Do you know the total of monotherapy and combined therapy reactions?

Dan

 

[D Bergy]

Not to change the subject, but when I hear mention of MS, I think this would be of interest to anyone who has MS.

I have copied the following post, with permission because I think this is one of the most important break throughs in MS research. I also think this pathogen makes sense for a number of reasons that I will not get into here. I have spent a great deal of time researching Lyme and MS as they always appeared to be related in some way. This pathogen is also a common Lyme co-infection, so the relationship has likely been discovered in my opinion.


I just spoke at lenght with someone at Galaxy Diagnostics in NC. For those not in the know, A veterinarian, Dr. Ed Breitschwerdt has done some amazing work, identifying bartonella in animals with a new patented test. Dr. Breitschwerdt is also an adjunct Professor of Infectious Disease at Duke University Medical School.

The better news is that there have been some research trials that have yielded results beyond expectation in humans. Testing and then treatment has been done, specifically on individuals who have been dx'ed with MS.. Many tested have been found to have bartonella and have responded beyond expectations with treatment.

The testing is two tiered. First by PCR and then culture grown to overcome sample bias. Then it will be DNA sequenced. There are over 22 named species of Bartonellis and as many as 30 species, some yet unnamed.

Galaxy is now working on antibiotic resistance studies. Their problem is funding and Grants have been applied for both with the MS Society and NIH.

They are working very hard at the present time to get the test out commercially. They never expected the huge results that they have had in trials.

The worse case that they have seen was a woman who was infected with Bartonella Melonagris (sp). contracted from a sheep. Bartonella has even been found in dolphins!

VALIDATION TESTING FOR HUMANS IS EXPECTED BY THIS FALL, CERTAINLY BY THE NEW YEAR!

This testing will be patient pay as the testing has not yet been FDA approved.

http://www.ksat.com/health/18915077/detail.html?taf=ant

Dan