This Is MS Multiple Sclerosis Knowledge & Support Community

My husband just pointed out to me last week that I still have my ice skates on the shelf in the closet. I can't even ride my bicycle anymore, although we have it in the garage and he used to ride it when my daughter was learning on her pink Barbie bike with training wheels; but the ice skates are especially useless since I not only can no longer use them, they are outdated in design, and for goodness sakes, we live in San Antonio: Hell freezing over seems more likely! But I have trouble giving up on myself. It goes further than "it's perfectly good" (my parents lived through the Great D) or "you never know when you could need that". It's more a case of "I used to be just like those other people".

When I was doing the Tysabri, I didn't suddenly become able-bodied, but it has been a dozen years now and lots needs fixin'. However, I did start to feel more like I was normal again, and I did have some recovery of my visual symptoms even for such a short period of treatment.

I don't exactly trust the situation, but I surely feel a glimmer of hope now!
Take care, everyone!
Ronnie

Ronnie, on the bike, get a 3 wheeled bike. Gary got one, just wanting to exercise, but felt a little aprehensive about the "granny" bike. You'd be surprised of how many perfectly normal people want to buy that bike! He likes it because when he stops, he doesn't have to worry about getting his feet down to catch his balance. He used to drive slowly up side of the house and lean in that direction. Quite funny to watch. He has always been a survivor and a fighter. I don't know that I could have adjusted as well as he.

Dear Amelia:
That sounds like a very good idea! Actually, I have asked my husband about getting a three wheeler. He is thinking about it. I guess the cost is prohibitive, and I doubt that our HMO would pay for it.

If the Tysabri is really going to reappear, and if I have a spurt of energy before the mind numbing heat of the Texas Summertime builds up (Summer starts very early here, and we are in a drought again), then I could get a bike this Spring! Mind racing, wind in my hair...

Meanwhile, I don't think I could pedal even a three wheeler right now. My legs have been kind of unreliable lately. Like I said, when I was on Tysabri, I seemed to be able to walk much better, and that includes more stamina. I was actually walking the dog to the end of our dead end street and back. Now I can only go about halfway, with a cane the whole way. That is about a block. We walk the dogs after dark when it is cooler, because any time the temperature is over 80 degrees F I have trouble with heat stress.

It was about 75 degrees F yesterday, by the way, and this is our Winter. I was born in Chicago, so I still find this odd.

Take care! I have to leave now to go study Photoshop CS2 to teach my classes tomorrow!
Ronnie

Gary got his at Wal Mart and the peddling is pretty easy. Gary has been paralyzed from the neck down too many times to even count, so I know about unreliable legs. Oh and the heat, we are in Mississippi. Our weather may even be a little stranger. On the bike... if you can't go far, go that far. The bike helps carry the legs their full range of motion. A therapist told Gary that was good to keep his legs stretched. It does help. When it is too hot here, Gary got a recumbent bike indoors. That's the kind that has a normal seat with a back and your legs are more stretched out in front of you. I have been known to tie his feet to the pedals to keep them on. Anything for exercise and MS has broke us financially. Not that we had that much to begin with. But we have learned to make do and create things for him.

Dear Amelia:
I will be looking at the tricycle-bikes!

The heat we have around here just shocks me, because I am used to muggy hot weather in the middle of the day in the middle of the Summer. When I moved here I encountered a pounding sunshine heat, that feels like a laser blast on the crown of my head, that lasts all the livelong day; then, at night, it is still hotter than it was during daylight hours on the same date in Chicago (my parents still live in Mundelein). It is probably just as hot and hotter in many places in the South, but I am a northern chick! I never expected this!

Perhaps the Tysabri will be released again before the real heat settles in, and perhaps I will be feeling more in control by then!

Tell Gary I admire his spunk!
Take care,
Ronnie

I don't know if it is spunk or just raw survival. He has a friend that has the cooling vest and cap. The kind that has those freezer things in it. Have you tried that? Heat bothers Gary more now, but has never been a big problem. Neither has fatigue. Don't know why, but very happy about it.

Dear Amelia (and Gary):
I wish I had one of those vests! I have some necktie-things that have Soil Moist pellets in them, that absorb huge amounts of water and slowly release it, sort of like having perspiration without the odor. They help, especially when I get warm while I am trying to lecture my class, or while I am standing in the kitchen cooking.

When I get overheated, I get very tired and have more and more trouble with my legs, balance, and ability to stand in one place. My legs get rubbery and I wobble a lot. I tend to make decisions which limit my mobility, in other words, I ask people to get stuff from the other room or to let the dogs out, so I won't have to walk anywhere.

I think I was able to move more freely and had less heat induced fatigue while I was treated with Tysabri. I suppose if I am treated with it again, I will be able to make the comparisons and see what is really happening! Otherwise, I am likely to view the past through those rosy glasses (don't we all)...

Ronnie

From Chicago Sun Times

Promising MS drug should not be withheld

February 18, 2006

BY ROBERT M. GOLDBERG


Bartira Tiburtius wakes up at night frightened. In 2001 the language teacher who lives in Chicago was diagnosed with multiple sclerosis, a disease where myelin, the protective insulation of the nerves necessary for healthy brain function, and then the nerves themselves, are slowly destroyed. That year, she had two horrible relapses where, as she recalls, "I lost my sight, I lost my ability to think clearly. I couldn't smell or taste food. I was waking up and not remembering what had happened. I was afraid to tell my doctor.''

She was already on a drug called Avonex when her doctor enrolled her in a trial for a new medicine, Tysabri. "After a few months, my balance returned, all the fatigue and horrible double vision went away."

Bartira wasn't alone. Dr. John Foley, chief of Neurology at Intermountain Health System in Salt Lake City, conducted studies with Tysabri and said he was amazed when he saw patients who had been wheelchair-bound by MS actually get up and take steps on their own after being on the drug for a short time. Another patient actually walked up two flights of stairs -- something he hadn't been able to do in two years, according to Foley. He recalls thinking: "This is anecdotal. But then we looked at the results after a year of experience. There were not only fewer relapses, but we also found a major reduction in enlarging or new lesions. I can't tell you how excited we were about this.'' Indeed, on average, Tysabri cut in half the risk of losing the ability to see, walk and remember.

Based on such robust results, the FDA approved Tysabri in November 2004 instead of waiting longer and asking for more people to be enrolled in more clinical trials. But last February, Tysabri was voluntarily withdrawn from the market after someone taking it in combination with Avonex, another MS drug, died from progressive multifocal leukoecephalopathy, a rare neurological disease. (PML is a problem only for people with compromised immune systems and is caused by a virus that is present in a dormant state in most people.)

A safety review was conducted by an independent committee of PML experts. Bartira was one of those evaluated as part of the review. She understood the need for the scrutiny. But she also remembers thinking at the time that other MS drugs carry dangerous side effects too.

Moreover, as Kevin Kam of Marketocracy notes: "[The study found] there is a 0.1 percent risk of contracting PML if you use Tysabri but so far, no cases of PML have turned up in patients who took Tysabri alone. To put this risk in perspective, a recent study showed that the mortality risk for aspirin is 0.2 percent." Meanwhile, MS causes about 53,000 relapses yearly and 5 percent of relapses cripple or kill their victims.

Patients considering Tysabri would be tested for PML through brain MRIs and molecular diagnostics. Data about how this and other MS drugs will be used to predict genetic and individual responses to a combination of MS medicines. That means patients will have continuously better information about benefits and risks over time.

It's hard to see why people with MS, armed with such information and new scientific tools, shouldn't be able to take Tysabri. Even the FDA acknowledges that a one-size-fits-all approach to drug approval is outdated in an era of individualized post-market tracking and personalized medicine. Its new approach to drug approval, called the Critical Path, relies on the same kind of personalized approach to drug approval and post marketing monitoring that Bartira and other MS patients have just gone through.

Bartira and Foley are hopeful the FDA lets MS patients have Tysabri back when the agency votes on its return to the market in March. Incredibly, some want to keep Tysabri from Bartira and other MS patients forever. Merrill Goozner, a senior fellow at Public Citizen, a group that lobbies against speedy approval of new drugs, said, ''Was the medical need for this drug [Tysabri] so serious, was its promise so promising, that it outweighed the need to take it through the normal clinical trial process?''

I asked Bartira how she would respond. Her answer was feisty, filled with hope, not fear or anger: "If someone told me Tysabri would take 10 years off my life, but make me feel like the way I am, I would do it. The decision is mine. Not my doctor's or the politicians. It is mine." Let's hope the FDA feels the same way.

Robert M. Goldberg is director of the Manhattan Institute's Center for Medical Progress in New York City, and recently testified before the U.S. Senate on health care policy issues.



http://www.suntimes.com/output/othervie ... ref18.html

As always, differing points of view about Tysabri exist!

Harry

____________________

S32.001] Immune Surveillance in Multiple Sclerosis Patients Treated with Natalizumab

Olaf Stuve, Christina Marra, Keith R. Jerome, Linda Cook, Seattle, WA, Petra D. Cravens, Sabine Cepok, Elliot Frohman, Ted Phillips, Gabriele Arendt, Dusseldorf, Germany, Bernhard Hemmer, Marburg, Germany, Nancy Monson, Michael K. Racke, Dallas, TX

OBJECTIVE: To test whether treatment of multiple sclerosis (MS) with natalizumab, an antibody against VLA-4, interferes with central nervous system immune surveillance, leukocyte cell numbers and cellular phenotypes in cerebrospinal fluid (CSF) and peripheral blood (PB).

BACKGROUND: Natalizumab was recently associated with development of progressive multifocal leukoencephalopathy (PML), a demyelinating disorder of the CNS caused by JC virus (JCV) infection.

DESIGN/METHODS: Cell numbers and cellular phenotypes in CSF and blood were analyzed in MS patients treated with natalizumab, untreated MS patients, patients with other neurological disease (OND), and HIV-infected patients. JCV DNA in the CSF and PB of these patient cohorts was quantified by kinetic PCR.

RESULTS: CSF total leukocyte counts, CD4+ and CD8+ T cells, CD19+ B cells and CD138+ plasma cells were significantly lower in natalizumab-treated MS patients compared with OND patients and untreated MS patients.

Natalizumab therapy decreased the CD4:CD8 ratio in the CSF to levels similar to that of HIV-infected patients.

JCV DNA was not detected in natalizumab-treated patients. Six months after cessation of therapy, low lymphocyte counts in the CSF persisted, whereas the CD4:CD8 ratio normalized. The patient with the highest total leukocyte, CD4+ and CD8+T cell counts in the CSF experienced a clinical relapse.

CONCLUSIONS/RELEVANCE: These data suggest that a low CSF CD4:CD8 ratio in natalizumab-treated patients may confer an increased risk of developing PML in these patients.

.
A South Bend woman joins the fight for the recirculation of Tysabri

Tysabri produced some miracles that have caused people to passionately fight to get the drug back on the market

03/03/2006

Story filed by NewsCenter16 Reporter Kimberly Torres

South Bend, IN

Some call Tysabri a wonder drug to fight off Multiple Sclerosis.
The Food and Drug Administration says it's not safe.

Now a South Bend resident is on her way to Washington D.C. to defend the drug on Capitol Hill. Tysabri was introduced in 2004, and it showed so much promise that the FDA prematurely approved it only to find it would produce lethal side effects.

On the flip side, Tysabri also produced some miracles and that's why people are fighting to get it back on the market. Heather Smith lives life at a relatively slow pace.

Diagnosed in 1998 with Multiple Sclerosis, she quickly became disabled. The disease often makes her choose between herself and her 2-year-old son. “I was at a point that I had a to pick, okay I’m I going to take a shower or should I hang out and play with Ezra this morning,” said Smith.

Heather became desperate for life, desperate for a cure. Eventually she tried the drug Tysabri and noticed a miracle after only two doses.

Heather went from wheelchairs and a walker to standing on her own with a cane.

“After being on this drug, my energy went back up and I was able to say "gosh I can take a shower and play with Ezra today if I wanted to. So to have a moment that I was actually improving was priceless,” Heather said.

Her world quickly came apart again, the food and drug administration pulled Tysabri from the market. Ken Fagerman of the St. Joseph Medical Center stated, “Approximately after a year introduced there were cases of PML which is a brain disease and there were a couple deaths it's now back under clinical trials which means it's under controllable trials, it can be used while we study it more.”

Tysabri was introduced in 2004, and it showed so much promise that the FDA prematurely approved it only to find it would produce lethal side effects. Until it's cleared, patients like Heather can't get their hands on their wonder drug, a drug that gave them hope of a new life.

“In the past year since I haven't been on Tysabri and still been taken the drugs that are available, my disease has progressed I would choose a fewer number of years of higher quality than a lifetime of poor quality life I want to be as healthy as I can for my son, he deserves that,” said Smith.

Heather Smith is on her way to get her miracle back. She left Friday night for Washington D.C. where the FDA is holding a hearing concerning Tysabri and whether it's safe or not.

Heather joins those around the country, which are trying to get it back on the market. For a drug that showed a 66% reduction in relapses for Multiple Sclerosis; you can understand why they fight.

http://www.wndu.com/news/032006/news_48379.php
.

Article from WSJ March 2

Paternalism Costs Lives

By HENRY I. MILLER, March 2, 2006; Page A14

Decisions about drug safety and efficacy are far from easy. Tysabri, a multiple sclerosis (MS) drug that was voluntarily withdrawn from the market last year after the appearance of a previously unknown side effect, illustrates some of the conundrums.

In advance of the publication of three critical new studies on Tysabri in this week's issue of the New England Journal of Medicine, a major news organization recently asked me, as a physician and former FDA official, whether I knew of examples of prescription drugs that have "efficacy but [also] serious safety issues." That is, I responded, the rule rather than the exception.

Obvious examples include the antimetabolites used for traditional chemotherapy. Because these drugs are no more than poisons administered in a way intended to be more toxic to cancer cells than normal ones, it is not surprising that their side effects are often serious and even life-threatening. When I was a medical resident three decades ago, hospital gallows humor included referring to BCNU, an experimental cancer drug, as "Be seein' you." Approved in 1977, it is still widely used.

A more recent example is aldesleukin, a drug that has offered new hope to victims of kidney cancer and malignant melanoma. It is highly effective in a small proportion of patients but exhibits significant toxicity. The patient information booklet warns that those taking the drug "frequently experience serious, life-threatening or fatal adverse events," including dangerously low blood pressure and reduced organ perfusion, impaired function of infection-fighting white blood cells, disseminated infection and autoimmune disease.

Antibiotics are another class of wonder drugs that sometimes manifest significant toxicity. Chloramphenicol, a drug that is effective against a wide spectrum of bacterial infections, causes rare cases of fatal aplastic anemia, so it is used only sparingly. The potent antibiotic gentamicin is often lifesaving but can cause damage to the kidneys, nerves and ears. And significant numbers of patients are allergic to other important antibiotics, including the penicillins and cephalosporins.

But let us return to Tysabri, only the sixth medication approved -- and the first in several years -- for the treatment of MS, a common and debilitating autoimmune disease that affects the central nervous system. The impressive results of the drug's testing in clinical trials -- the frequency of clinical relapses reduced by more than half -- induced the FDA to grant accelerated approval in 2004. By the time that several thousand patients were being treated with Tysabri, however, three had contracted progressive multifocal leukoencephalopathy (PML), a rare neurological disorder caused by a virus. (Because the drug suppresses certain components of the immune response, regulators, clinicians and the product's developers had from the beginning been sensitive to the possibility of infections as a side effect.) Immediately -- some would say prematurely -- the manufacturers of the drug voluntarily halted production and distribution and withdrew Tysabri from the market. MS patients and many neurologists were bitterly disappointed.

The three clinical studies reported this week in the New England Journal of Medicine bolster our confidence about the safety and efficacy of Tysabri. In a study of almost a thousand patients that compared Tysabri to placebo, the drug cut the rate of clinical relapses by 68% (to 0.24 from 0.75), reduced by 83% the number of new or expanding brain lesions found on MRI, and slowed the clinical progression of disease. (The other currently used drugs for MS lower the occurrence of acute relapses by roughly one-third.) Similar results were obtained in a second trial which compared two-drug therapy with Tysabri plus interferon beta-1a to the interferon alone.

Finally, a third study found no additional cases of PML in more than 3,000 patients (exposed to an average of 17.9 monthly doses) who had participated in clinical trials of Tysabri. The investigators concluded that the incidence of this serious side effect is approximately one in a thousand patients treated with the drug.

However, it should be noted that all three of the original cases of PML occurred in patients treated with interferon beta or other immunosuppressive agents in addition to Tysabri, so the risk might be significantly lower in patients treated with Tysabri alone.

The "safety" of a drug is a relative thing. Safety and efficacy, the two criteria required for marketing approval of a drug, are inextricably linked. The judgments of regulators (and practicing physicians) require a global and often difficult calculation of risk and benefit, including consideration of what alternative therapies are available. For a given drug, we are willing to tolerate greater uncertainty and more severe side effects for a potential cure for pancreatic cancer or AIDS, for example, than for a new drug that treats heartburn. When FDA grants marketing approval, the drug is deemed to be sufficiently safe and effective to be used for the conditions on the label.

In light of the just-published data -- to which the FDA should have had access months ago -- it is clear that this drug belongs back on the market, probably with new warnings about PML in the labeling.

The notion that the FDA should "err on the side of safety" sounds like a tautology but is an affront to patients with incurable or poorly treatable diseases: For them, there is no safety in the status quo, and we only damage them further with paternalistic public policy that prevents individuals from exercising their own judgment about risks and benefits. If the FDA must err, it should be on the side of patients' freedom to choose.

Mr. Miller, a physician and fellow at the Hoover Institution, headed the FDA's Office of Biotechnology from 1989 to 1993.
.

Better,

The one big difference between the very toxic drugs that Dr. Miller mentions in this article and Tysabri is that the docs are very aware of what dangers to look for with these toxic drugs. Perhaps had Biogen done a lot more testing with Tysabri, the docs would be in a much better position today to determine what may happen. Hopefully when Tysabri is re-approved, the patients will be monitored very carefully by their physicians and thus avoid potential problems.

Harry

Big Whoop! Biogen didn't do what they should have at first and I dare to say, many ohter drugs and drug companies have done this, are doing this, and will continue to do this. It all boils down to the patient being involved with their treatment, whatever it is. We are told a lot of things are SAFE and they are not. Shame on ME if I don't do my homework and know everything about the drug, on my own, not by just DR's. Time to quit looking back at what Biogen DID and look at what will be DONE. Looking forward to the RETURN of Tysabri

Amelia,

What is it they say....if you want to know what is going to go on in the future, examine what happened in the past. When it comes to drug companies' actions, I sure hope that Biogen doesn't follow this little saying because MS patients have had to put up with enough from them so far!

I agree with you in that patients have to take some control when it comes to determining their medications. We know that the docs don't always have enough time (not a great excuse) to work with the patients on this but wouldn't it be nice if we could at least believe everything that the drug companies were telling us!!

Harry

Yeah, but unfortunately, I don't things will change for the good. Too many greedy people running companies of all kinds that are looking at the almighty dollar. Just look at all the price fixing that went on with large corporations. Drug companies fall into those catagories too.