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This is my opinion only mine and my husbands. He said he would take the risk to take Tysabri. I have posted that before. His aunt took a type of interferon for Hepatitis C. It was awful what it did to her. Gary took Betaseron, and the effects were milder, but still pretty bad. He tolerates Copaxon well and it seems to work okay. But you know NOBODY knows the effects of all the treatments for MS long term. Not one person here knows what they might develop due to the CRABs or the chemo or anything else. It is as uncertain as the disease itself. Many if not most of the MSer's taking the CRABs and other treatments experience the effects of the drugs right now. It is known that interferons can cause severe liver damage in people, and sometimes failure. But the PML issue has yet to show up in anybody else. That sure is a lot of people in the Tysabri trials with only 2 showing issues. Everyone says that they are the ones on it the longest. Was this stage of the trial only for 2 people? Summary: No one wants anything bad to come out of a treatment. But when there is hope, the patient themselves should be able to decide the issue, in this particular case.

Amelia,

The two patients who got PML were on the combo treatment for 37 and 28 months respectively. Perhaps they may have also been part of the Phase II trials but I have never heard any reference made to that.

I don't know how many other trial patients have been on Tysabri alone or combo therapy for longer than the above two people. If few others have then one of the problems in bringing back Tysabri soon is trying to determine if longer term use (ie: more than 24 months) may have played a part in the problem. It may not have but until they come up with some answers Biogen, I doubt, will allow it back.

The frustration level that many MS patients are experiencing over this situation is immense....but I don't have to tell you that!!

Harry

Amen to that! LIke I have said before, it is just so frustrating. It boils down to the disappointment of something better comes along and then the hope is yanked out from under you.

Elan and Biogen Idec Announce TYSABRI Update

Wednesday March 30, 4:56 pm ET


DUBLIN, Ireland and CAMBRIDGE, Mass.--(BUSINESS WIRE)--March 30, 2005--Elan Corporation, plc (NYSE: ELN - News) and Biogen Idec (NASDAQ: BIIB - News) announced today that their ongoing safety evaluation of TYSABRI® (natalizumab) has led to a previously diagnosed case of malignant astrocytoma being reassessed as progressive multifocal leukoencephalopathy (PML), in a patient in an open label Crohn's disease clinical trial.

In light of the two previously reported cases of PML in multiple sclerosis clinical trials, Elan and Biogen Idec initiated an additional comprehensive safety evaluation of TYSABRI clinical trial patients. In the course of this safety review, the companies identified a case warranting reassessment in an open label Crohn's disease clinical trial. In July 2003, the case was reported by a clinical trial investigator as malignant astrocytoma. This diagnosis was confirmed at the time by histopathology. The patient died in December 2003.

As part of this ongoing safety review, the companies, in agreement with the clinical trial investigator, reassessed the case. Following this additional evaluation, the diagnosis is being reassessed as PML. The patient had received 8 doses of TYSABRI over an 18 month period and prior medication history included multiple courses of immunosuppressant agents.

Elan and Biogen Idec's comprehensive safety evaluation concerning TYSABRI and any possible link to PML is ongoing. The companies are reviewing clinical trial data, working with investigators to evaluate the approximately 3,000 patients in multiple sclerosis, Crohn's disease, and rheumatoid arthritis trials, and working with PML and neurology experts. The results of this safety evaluation will be discussed with regulatory agencies to determine possible re-initiation of dosing in clinical trials and future commercial availability.

On February 28, 2005, the companies announced that they had suspended marketing of TYSABRI in multiple sclerosis and dosing in all clinical trials based on two previously reported cases of PML, a rare and frequently fatal, demyelinating disease of the central nervous system

http://biz.yahoo.com/bw/050330/305833.html?.v=1

beginning to sound like Avonex or any other immunosupressant is the culprit. And with a lot of study, maybe you don't need to be on Tysabri for long periods.

My conclusion is the opposite.
This patient wasn't on combo therapy, the immunosuppressents he/she got were before tysabri.
Clearly no avonex was involved.
This is really bad news for all of us that hoped PML cases arose due to the combo.

Guy

But they were on an imunosuppressant before the Tysabri and the MSr's were on Avonex before the Tysabri. Can Avonex be considered an immunosuppressant? I am just asking because I am not a DR or nurse. Just a curious family member. But yes, it does probably delay more or discontinue Tysabri because someone besides MS had PML. Very discouraging. I do agree.

I'm an Avonex user and after more than a year on this drug I haven't been able to clearly understand if Avonex suppresses the immune system, modulates it, or, does much of anything for some people with MS.

From the package insert and fine print which accompanies Avonex, the insert with an issue date of 10/04 contains the following statements:

The specific interferon-induced proteins and mechanisms by which Avonex exerts its effects in multiple sclerosis have not been fully defined.

and, equally important I think

Safety and efficacy of treatment with Avonex beyond 3 years is not known.

I believe someone posted that at least one of the previous individuals diagnosed with PML had been on the Tysabri-Avonex combo for about 37 months, slightly more than 3 years. Because the mechanism of action and safety of Avonex beyond 3 years is not known, I still support a review of Avonex.

This is not to alarm people on Avonex. I'm still injecting. I make this point because I think the statements about what the FDA has posted about PML and interferons and what the FDA has in fact posted have both been very carefully worded, that's all.

The potential role of Avonex in this should not be easily dismissed IMHO if they can't explain how it works and the safety and efficacy beyond three years is not known.

Sharon

Guy,

I agree with you that this is not good news for Tysabri with the hope of seeing the drug being available again in the immediate future.

We now have a third confirmed case of PML with use of the drug in a relatively short period of time. With the patient on immunosuppressants prior to starting on Tysabri, they will obviously be looking to try and establish some connection. But I'm afraid that this is going to take a fair amount of time.

If you look at the history of MS patients, many have taken a CRAB or been on steroids or perhaps some kind of chemo. And all of these drugs have an effect on the immune system. Will that perhaps eliminate them from ever using Tysabri? Who knows but a lot of research is going to have to take place now.

Harry

.
NCB Report

March 31 2005

A third case of PML has been diagnosed in a patient who was treated for 18 months
with Tysabri monotherapy for Crohn's therapy. The patient who died in December
2003 had previously been diagnosed as having died of malignant astrocytoma, this
diagnosis has now been reassessed as progressive multifocal leukoencephalopathy
(PML). The medical background of the patient is complex and reflects treatment with a
series of immunosuppressive drugs before treatment and during treatment with
Tysabri.

• This is the first case of PML seen in a patient treated with Tysabri monotherapy and
therefore rules out any firm link with combination treatment with AVONEX, which was
the best case outcome for Tysabri. However like the other cases where PML has been
seen this case is complicated by the fact that the patient had received other
immunosuppressive medication - in this case its reported that the patient had received
8 doses of Tysabri and had also received multiple doses of immunosuppressive
agents. We understand that the patient had previously been treated with Remicade
and steroids and was treated for approximately a five year period with Azathioprine, a
transplant drug which is itself associated with PML as a side-effect. The patient
received 3 doses of Tysabri in the Crohn's disease induction trial, was subsequently
randomized to the placebo trial arm for 9 months and received placebo, before
returning to Tysabri treatment for 5 doses in an open label study.

• Given the complex treatment combination used in this patient (before treatment with
Tysabri) and the fact that the patient was exposed Azathioprine in particular and also
Remicade, both of which have been associated with PML and demyelinating disease a
clear link with Tysabri monotherapy may not exist and the fact that this patient received
Tysabri monotherapy may be found to be unrelated to the PML outcome.

• The companies continue to methodically review the patients in the Tysabri clinical trials
for PML and we estimate the review will be completed over the next 4 weeks. Post
completing the review Elan and Biogenidec will meet the FDA to determine the
possible re-initiation of dosing in clinical trials and commercial availability of the drug.
.

why is someone with such a complicated and risk-prone medical history allowed to participate in a clinical trial of a potentially dangerous product? FIVE YEARS of treatment with azathioprine, a powerful transplant drug?!?

From medline:

"While you are being treated with azathioprine, and after you stop treatment with it, it is important to see your doctor about the immunizations (vaccinations) you should receive. Do not get any immunizations without your doctor's approval. Azathioprine lowers your body's resistance to infections. For some immunizations, there is a chance you might get the infection the immunization is meant to prevent. For other immunizations, it may be especially important to receive the immunization to prevent a disease. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have recently taken oral polio vaccine. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Azathioprine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding"

Azathriopine and PML:

" A case of progressive
leukencephalopathy (PML) after a four year
azathioprine therapy with difficulty in
urinating, articulation, spastic hemiplegia
and eye movement malfunction was reported
(Schnider,1991)."

Another relevant citation:


Signature: Case Rep Clin Pract Rev, 2003; 4(1):38-42

Received: 2002-03-15
Accepted: 2002-10-07

Progressive multifocal leukoencephalopathy in a renal transplant recipient: the first case in Poland?

Jacek Borawski , Iwona Chlebińska, Beata Naumnik and Michał Myśliwiec
Summary:
Background: Progressive multifocal leukoencephalopathy (PML) is a rare, rapidly progressive, demyelinating disease of the brain caused by polyoma JC virus. It occurs in immunocompromised patients, including those after solid organ and bone marrow transplantations. We present the clinically diagnosed case of PML in a renal allograft recipient.
Case Report: A 34-year-old male kidney transplant patient receiving triple-drug (cyclosporine, azathioprine, prednisone) immunosuppressive treatment for 60 months complained of progressive visual loss, vertigo and weakness of the hand. He had congenital strabismus, severe hyperopia, a freshly diagnosed corticosteroid-induced cataract, and normal retinas and optic disks. Magnetic resonance imaging of the brain showed large, multifocal, asymmetric, nonenhancing white matter lesions in the periventricular and subcortical areas, which were strongly characteristic of PML. Both cytomegalovirus IgM antibodies in serum and DNA in cerebrospinal fluid were detected, and the patient was treated with gancyclovir. He was also switched to mycofenolate mofetil because of the possibility of cyclosporine-induced leukoencephalopathy. Despite the therapy, the patient showed relentless neurobehavioral deficits, and died in coma 5 months after the presentation.
Conclusions: PML is an infrequent but fatal disease. Renal and other transplant recipients with neurobehavioral disturbances should be promptly investigated for PML and other demyelinating diseases of the brain. Special attention should be paid to those with a corticosteroid-induced cataract and progressive visual complaints.

Arron,

Arron wrote:why is someone with such a complicated and risk-prone medical history allowed to participate in a clinical trial of a potentially dangerous product? FIVE YEARS of treatment with azathioprine, a powerful transplant drug?!?

Kind of makes you wonder, doesn't it? I don't know just who makes the final decision on what patients get into some of these clinical trials but are we again seeing Biogen trying to rush a drug into another market?

You would think that, due to the very nature of how Tysabri works, anyone who had a history like this patient did, would not have been allowed in this trial.

It could also be that Tysabri is the drug that "pushes" the patient's immune system beyond the brink in handling infection when other immunosuppressent drugs have been used previously. I don't like to sound like a broken record but I've stated all along ( as did a number of other docs/researchers) that Biogen was going too fast with Tysabri and needed more data before getting FDA approval. And it also makes me wonder if officials in the FDA had their heads in the hand when they went through the approval process with this drug!

Harry

....I don't know just who makes the final decision on what patients get into some of these clinical trials....

Hi, Harry! It's the clinical trial sponsor who determines if someone is accepted or not for the trial. I know because I was going to be in a clinical trial (and remember that my medical records and examinations, which I had not seen at the time, shows NO evidence of me having MS at all - THREE clean MRIs, clear CSF with no o-bands, etc.), and at one point, my first neuro must have realized he'd be accused of having misdiagnosed me, because he called me in a tizzy and said "we have a problem". We discussed how or if the "clinical trial people" would say I could be in the trial or not. I asked him what the protocol was that they had come up with. Anyway, it ended up that he decided he'd call the sponsor (a pharma company) and explain my test results and see if I met the criteria. Believe it or not, they told him that I was - and I quote exactly - "the perfect patient for the clinical trial". Uh.........someone who doesn't even show clinical evidence of HAVING MS is the "perfect patient"? Even my neuro was a little surprised. After a while, though, once I myself started having some doubts about many things, I withdrew myself from the trial.

We've talked before on this thread: http://www.thisisms.com/modules.php?nam ... ight=#6888 about Biogen's irresponsibility regarding the Tysabri clinical trials. I looked up their criteria that you had to meet to be in the trial:

Ok..........here I go, huh?

Ok.........just what WAS the criteria to meet for the Tysabri/Avonex trial?

Quote:
http://www.clinicaltrials.gov/ct/show/N ... 66?order=9

Eligibility

Ages Eligible for Study: 18 Years - 50 Years, Genders Eligible for Study: Both

Criteria

Male and female subjects between 18 and 50 years of age who have a diagnosis of relapsing remitting multiple sclerosis

AND

who have been treated with Avonex for at least 12 months prior to study entry.

Ok......No comment. All I can say is how interesting!

Oh, I guess I'd have to also say "that's it?"

Hey, I've seen people be diagnosed and un-diagnosed with RRMS constantly! What are the determining factors that are to be used in order to adequately determine that clinical trial participants have RRMS in the first place in order to be eligible for this trial? Based on what or which particular test results or diagnostic criteria? Poser, McDonald, Schumacher's? LP, MRI only, diagnosis by exclusion, the doctor's "gut feeling", all of the above? ....

Anyway, this whole thing makes me ill. Especially now that I've been removed from medical care and confusion for a while now, and can view things more objectively (and in hindsight).

How many people are in clinical trials with these strong drugs that don't even have MS at all? A few months ago, I would have said it was highly unlikely that anybody could be misdiagnosed with having MS.

Now I'm beginning to see that it is probably more prevelant than we'd like to think. Scary, huh?



Deb