Newswise — People with multiple sclerosis who stop taking the drug natalizumab may experience a rebound increase in disease activity, according to a study published September 12, 2007, in the online edition of Neurology, the medical journal of the American Academy of Neurology.

The study involved 21 people who had MRI scans of their brains taken before taking natalizumab and again an average of 15 months after receiving the last infusion of the drug. The drug is given by IV infusion once a month. The participants were divided into two groups: one group took the drug for an average of three years, and the other group took the drug for an average of two months.

The participants developed more than three times as many brain lesions, or areas of damage in the brain that are a marker of MS disease activity, in the 15-month period after discontinuing the drug than they had developed before they started taking the drug. The results were most pronounced for those who took the drug for only a short time; they developed five times as many brain lesions after stopping the drug than they did before they started taking it.

More research needs to be done with larger numbers of patients before any recommendations can be made about use of the drug, according to study author Machteld Vellinga, MD, of VU University Medical Center in Amsterdam, the Netherlands. “For now the recommendations remain the same—patients and their doctors should choose the most applicable treatment for them,” she said.

Vellinga said it’s not clear why discontinuing the drug would lead to increased disease activity, although an earlier animal study showed a similar result when rats with an animal model of multiple sclerosis were given a drug that suppresses the immune system.

The study came about because use of natalizumab was suspended in 2005 after three people participating in clinical trials for the drug developed a rare, often fatal brain disease called progressive multifocal leukoencephalopathy.

“All of our patients had an MRI shortly after the drug was suspended, and our neuroradiologist noticed that in some patients a considerable number of new lesions developed on their MRIs in the following year,” said Vellinga. “We decided to do a formal analysis to see if this was actually the case.” Vellinga noted that the results need to be confirmed in independent groups of patients.

The drug was reintroduced in 2006 with specific guidelines for its use and to monitor patients for signs of progressive multifocal leukoencephalopathy.

The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as epilepsy, dystonia, migraine, Huntington’s disease, and dementia. For more information about the American Academy of Neurology, visit http://www.aan.com.


http://www.newswise.com/articles/view/533267/?sc=rsmn

Yuck!

Well I guess the drug hasn't been out long enough to determine any real patterns yet, but this makes me wonder if Tysabri is just temporarily "holding back" the disease process.

I suppose it doesn't matter much if a person stays on the drug forever, but last I heard, some people were advised to take breaks at some point in time. Anyone know if that is still "the plan" for some?

Cherie

Hi Pantos, how are you doing? We haven't heard from you in awhile.

I had heard that about Tysabri before...sheesh, it's like pick your poison and take your chances.. I also heard that if you had been on TY for a short time, then got off of it, then restarted it, that it didn't work as well???

Thanks for posting.

If you look hard enough at small groups of patients, you can come up with a group to fit your needs.

I take issue with this "study". Does it tell us what treatment these patients received after they went off Tysabri? Were they left untreated for 15 months? Did they have any steroids, CRABs, Cellcept, Imuran,Novantrone? Isn't going off a drug an obvious restart to disease activity?

MS is CHRONIC. It will reappear and worsen if treatment is stopped. That would be ANY treatment.

This issue has been studied in REAL studies.

How about this one?

http://www.emea.europa.eu/humandocs/PDFs/EPAR/tysabri/H-603-en6.pdf

River...or anyone....

I am having a hard time following what this really means.
In the pdf article you linked there seems to be a contridiction, or am I reading this wrong?

You quoted supportive phase II study
Study MS 231

But on page 23 I found this:

• Rebound after discontinuation
Data from the phase II study MS 231, where patients received 6 months of active treatment and a follow-up of additional 6 months after treatment discontinuation, suggested that there might be the danger of a subclinical rebound of MRI lesions, exceeding those in the placebo group.

Now I am really confused.

So, it seems they noticed this pattern with the mice, then with the original Phase MS231. Next they noticed a pattern with patients, and followed up with a small study that the same observation . . .

I'm thinking the evidence is becoming more convincing, but I certainly hope they are REQUIRED to do more studies, with a bigger group.

Cherie

The difference between that study, and the most recent findings is that:

- the follow-up period was very short; 6 months
- that study focused on gadolinium enhancement (which is said to be a transient phenomenon of MRI disease activity)
- this most recent study focused on the cumulative burden of disease (T2 lesions)

Cherie

This "study" really doesn't say too much other than these patients ended up with a lot more brain lesions...which means just what in MS?!

Lesions come and go in MS patients and there is little if any correlation between lesions and symptoms. It's not the number of lesions, it's the location of them that is important.

The study fails to mention if these patients encountered an increase in symptoms and that I find a bit irresponsible.

Prior to Tysabri being approved the first time around, there were rumours of this rebound effect with some patients who had to stop the drug for various reasons. In the Affirm and Sentinel trials, it was determined that 6% of the patients ended up with constant, high level antibodies and they had to stop treatment. I've never heard if these patients ended up getting an increase in lesions.

I'd also be interested in hearing if potential Tysabri patients are advised of this possibility if they have to stop taking the drug.

I'm afraid there is still a lot unknown about this drug and now that thousands of patients have used it for 6 months, we are likely going to start seeing some complications. Let's hope that the MS patients who are using it don't run into any major problem.

Harry

Amen Harry....I worry too!

When I first began looking into taking Tysabri I spent quite a bit of time on the different forums, and what I found were lots of people who'd been forced to discontinue the drug and were on a faster downward spiral than before they started taking it. That was before it even came back on the market.

I am in the middle of my first month and I like it. I feel nearly normal now. So I'm holding my breath that this thing wont be taken off the market again. Still, given this drugs history, it is all too likely, in which case, I may have to face the increased speed of disease, I am trying to formulate a what if plan.


Any thoughts on the proactive side of this? What in your opinions, would be a reasonable preventive action in the case I am forced to stop taking Ty?

Katty