Review of PML and Tysabri
 

Scary that the MR imaging of PML is indistinguishable from MS and that PML deficits could be permanent and could alter our immune systems irretrievably (wonder what that means for a person's future MS course?) Also that, while early intervention with treatments might help you to survive PML, the damage left could be permanent. Scary too that length of time on Tysabri might be a risk factor in development of PML.

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

Neurologist. 2006 Nov;12(6):293-298.

Review of Progressive Multifocal Leukoencephalopathy and Natalizumab.

Aksamit AJ.
From the Mayo Clinic College of Medicine, Department of Neurology, Rochester, Minnesota.

BACKGROUND:: Progressive multifocal leukoencephalopathy (PML), a destructive demyelinating infection which lytically infects oligodendrocytes, has occurred in patients treated with natalizumab. Magnetic resonance imaging (MRI) scan imaging of the brain gives clues to diagnosis but is nonspecific in distinguishing multiple sclerosis from PML. Spinal fluid detection of JC virus is specific but incompletely sensitive. Associated immunosuppression is typically of the cell-mediated type but can be poorly defined on clinical grounds.

REVIEW SUMMARY:: It is apparent that natalizumab is a predisposing factor for developing PML from the 3 cases of natalizumab-treated patients. There is no reliable presymptomatic way to detect PML or JC virus infection of the brain by virologic or imaging surveillance techniques. One patient with multiple sclerosis and natalizumab treatment has survived, indicating that withdrawal of antibody, possibly in combination with antiviral therapy, may permit survival. However, immune reconstitution disease is a risk after immune restoration and withdrawal of natalizumab. PML deficits would be expected to be permanent. The estimate of incidence of PML in natalizumab-treated patients is 1 per 1000. The duration of natalizumab treatment may be an independent risk factor for development of PML.

CONCLUSION:: PML, a usually fatal neurologic infection, should be considered as a risk factor when using natalizumab. The treatment of multiple sclerosis patients with natalizumab is a matter of informed risk, individualized for each multiple sclerosis patient.

PMID: 17122725 [PubMed - as supplied by publisher]

Thanks for posting this, Pantos. I don't know how everyone else feels, but, for me, the possible benefits of Tysabri, do NOT out weigh the risks of PML.:eek:

I realize that it's a personal decision, but I still worry about those who have chosen to take Tysabri. If PwMS hadn't begged for it to be returned to market, I don't think it would have been.

I pray for all of you on Tysabri, to have the best symptom relief you can get with no bad side effects.

Sally,

Those who know me from various MS Forums know of my high doubts about the efficacy of Tysabri. After initially being excited about this new drug back in the summer of 2003, that feeling quickly disappeared as I followed Biogen's introduction of it and started to learn more and more about its dangers.

I too feel that its benefits don't outweigh the risks but at the same time respect anyone's decision to use it...IF they are told about ALL the pros AND cons about the drug. Tysabri is a monoclonal antibody that tampers with the immune system....and that can spell "trouble" in the long run.

I sure hope the many that choose to use it don't run into these possible problems. The Mayo Clinic didn't post this information for nothing!

Harry

None of the three PML cases occurred in patients taking Tysabri in monotherapy, other than the one patient who had been on immunosupressants for a protracted period of time. Although some argue that the immunosuppressed patient had been off those drugs for months, there is no proof that his immune system was functioning normally at the time of his Tysabri infusions.

Every day, the 1:1000 figure becomes more outdated, as thousands of new patients begin Tysabri infusions. I would guess that, should the trend of PML-free therapy continue for a year, many more people will begin to believe in the safety of Tysabri.

I'm afraid I will have to respectfully disagree with you on the Crohn's patient who was indeed on a monotherapy with Tysabri. He had stopped using Infliximab 20 months earlier and hadn't used Azathioprine for 8 months. He was in generally good health (other than from the typical symptoms from Crohn's which he endured for 28 years) and went fishing and hunting.

The JC virus only appeared in his blood during his monotherapy Tysabri use between Feb-June 2003. In one NEJM article, the reps from Biogen/Elan state they asked the physicians who controlled the trial to review his case while in their own article, the physicians say they informed Biogen/Elan first, after knowing about the 2 MS patients who contracted PML!

The family of the Chron's patient was never originally informed about the cause of his death although the Biogen/Elan and the docs knew and stated such in the NEJM article. The family was informed by their doc in April 2005 and then told about the PML cases. The family ran up against roadblocks from the trial docs and Biogen/Elan when they asked to review the all the medical files. When they finally succeeded in being able to do so they were told "try not to make a big fuss about this"!!

This is another reason why I don't think we are being told everything by Biogen/Elan and the docs when it comes to Tysabri and PML. Biogen/Elan have been hanging their hat on the fact that PML did not occur in any monotherapy with Tysabri. The Crohn's patient situation looks like this isn't likely the case.

Harry

When Money is the motivation, it's difficult to believe anything that is said. The slanted trials, the reporting of questionable end results of those trials and the positive words drooling from the mouths of big Pharma.:rolleyes:

The FDA should be protecting the people from this sort of salesmanship and find the truth for us, instead of going along to get along with Big Pharma.

The people are now informed of the dangers from Tsabri, although, I am sure, not fully informed. We are only seeing, as always, what they want us to see.

Sometimes I feel like we are lambs being led to a slaughter.:(

Hey Harry,

As you know, I've been a little freaked out at the number of patients who started and stopped Tysabri on its first approval and are now showing severe allergic reactions to it once they start the infusions again. Despite the warning to discontinue its use at that point -- listed in Tysabri's own prescribing info -- they're setting up those reactive patients to receive Benadryl infusions in conjunction with Tysabri to counteract future allergic reactions. Mind boggling...

Also on the Tysabri site they point out that starting, stopping, and starting it again may produce this type of hypersensitivity with monoclonal antibodies.


"The long-term immunogenicity of TYSABRI® and the effects of low to moderate levels of antibody to natalizumab are unknown. Experience with other monoclonal antibodies suggests that patients who receive therapeutic antibodies after an extended period without treatment may be at higher risk of hypersensitivity reactions than patients who received regularly scheduled treatment. It is not known if this will occur with TYSABRI (see WARNINGS, Hypersensitivity and ADVERSE REACTIONS, Infusion-related Reactions)."


This thread's discussion about the Crohn's patient reminded me of something else about his case that was documented in the NEJM article, so I pulled out my copy (I have dozens of Tysabri articles printed up and filed here). The Crohn's patient who came down with PML had also stopped Tysabri for several months and resumed the treatment later.

No JC virus appeared during any of his other drug treatments which, like Harry said, had ended months before the JC virus was finally noted in his system. No JC virus appeared during his first 3 Tysabri infusions or during the 9 months he was on placebo.

But...the JC virus showed up immediately after his Tysabri infusions resumed and the viral load increased substantially during the 5 infusions before he was admitted to the hospital. It's always bothered me that the Crohn's patient came down with PML after fewer infusions than the other patients, especially since he had been on placebo for much of the trial.

It was reassuring to think that Tysabri must be pretty safe for at least a couple of years, but now I think I'm even more freaked out. What if there's something else going on entirely? They just don't understand these drugs yet. :(

P.S. Many of us already knew that there is no test for PML, no treatment, and that its damage is permanent. I just don't think that fact has been stressed enough to potential patients who haven't followed the whole saga as closely as we have.

Check out the "Patient Medication Guide" and the "Product Information" on the Tysabri website
http://www.tysabri.com/product-information.html

Hi Susan,

Reading your post just re-emphasizes the major concern I've always had with this drug...and that is the way Biogen/Elan rushed its introduction into the marketplace!

Even though they were aware of the dangers of a monoclonal antibody and certainly didn't have any kind of reliable safety data, Biogen/Elan focused solely on the so-called beneficial stats of Tysabri from one year data from 2 of 99 world-wide Phase III trials going on at that time. That's what they used to convince the FDA to accelerate the approval of the drug while at the same time making several press releases on how wonderful this drug was going to be for all MS patients. The problems that were happening were swept under the carpet and got little if any attention.

I really hope that MS patients don't pay the price for this kind of drug marketing.

Harry

Don't forget the gushingly negative comments of competing Big Pharmas.

IMO, the efficacy and safety of Tysabri is no less than its competitors, and its potential to provide relief is far greater. I think the number of patients already enrolled is a testament to their confidence.

:rolleyes:


Have you noticed that the talking heads who were so visible prior to Tysabri's re-approval have disappeared? Maybe, once there was no chance of queering the re-approval, the hired guns lost interest in the "safety profile" of Tysabri? You seem to be the last guy carrying the banner.