Tysabri and progressive MS

[NINOU]

I have a progressive MS and I 'm really sad when french neuros said to me Tysabri is not for you.
Is there anboby treated with Tysabri and having progressive form ?

Help !

[lollipop]

I have taken Tysabri 7 times now with no improvement. Going to see neuro today to discuss other options... if there are any. Otherwise, I guess I'll have to accept my future .

[RuSmolikova]

I am afraid there is no one with PP-MS on Tysabri.
The Food and Drug Administration (FDA) gave an approval of TYSABRI® (natalizumab) as a "monotherapy treatment for relapsing forms of multiple sclerosis (MS)". And European Commision did the same on June 2006.

http://www.elan.com/Images/TYSABRI-pi_tcm3-7614.pdf
(see page 2 - part 1.1.)

[marcstck]

Actually, there have been a few PPMSers put on Tysabri. I am one of them. I did four doses of Tysabri from September through December of 2006. Unfortunately, the drug did nothing for me. As a matter of fact, I feel like it may have made me worse.

Although the drug is officially approved only for RRMS, many of us progressives have not been officially labeled as such by our neurologists, because that label severely curtails the doctor's ability to try different treatments (because of insurance). I've ran into several other PPMSers on various boards that have also tried Tysabri. I don't believe any have found it to be helpful...

My doctor is currently trying to get me Rituxan on a compassionate use basis. This means that Genentech would supply the drug for free for use on an off label basis. I should find out something within the next few weeks. I'm hoping to see positive results from the Rituxan PPMS trials, which should be released sometime within the next three months.

[lollipop]

Went to see neuro. He explained that he thought Tysabri hasn't worked for me because my MS isn't really inflammation, but rather scarring. What?? Then he went on to say that Rituxan hasn't been approved for PP, but only Novantrone has. So now he wants to try that. I don't know if the risks are worth it?! Anybody? I also wonder if the Tysabri has made me worse... or if the PP is just doing what it's gonna do anyway.

[msladyinca]

Hi everyone,

In the US, Tysabri is approved for "relapsing forms of MS". These include Relapsing/Remitting, SPMS with relapses, and Progressive Relapsing. These are all in the inflammatory stages of MS.

Tysabri is not currently approved for SPMS without relapses, nor Primary Progressive MS, as these two stages of MS are in the demyelinating stages.

In the EU, Tysabri is approved for RES (Rapidly Evolving Severe Relapsing/Remaining MS, which is similar to the US definition of Progressive Relapsing MS). The definition of Rapidly Evolving MS is as follows:

RES is defined by two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI)

OR

a significant increase in T2 lesion load compared with a previous MRI.

See: http://www.nice.org.uk/nicemedia/pdf/TA ... fguide.pdf

I am scheduled for my 20th Tysabri infusion next week, and although I am not seen the same improvements as the others are, Tysabri is working for me as it is keeping my MS stable. I have been on Tysabri therapy for over 17.5 months now, and I have not had a relapse nor any disease progression since restarting Tysabri in October, 2006. The Tysabri label states in part: "TYSABRI® is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations."

In addition, I just saw my neurologist two weeks ago and she authorized another six months of Tysabri for me, woo hoo! I also had my regular six-month liver enzymes checked, and they came back perfectly normal.

To marcstck, I do not believe that Rituxin can be prescribed off label for any form of MS as it is still in trials. The reason for this is Rituxin also carries a Black Box Warning as 24 people have developed PML while on Rituxin therapy, resulting in two deaths directly linked to Rituxin.

Hope this information helps... all my best to everyone,

Lauren

[marcstck]

I was on the phone with Genentech today, Rituxan can indeed be prescribed off label for MS. It is in trials for both RRMS and PPMS, but that does not disqualify its use off label for either of those two conditions.

Unfortunately, my annual household income exceeds the limits set by Genentech for the compassionate use of the drug. I'm going to file paperwork with them explaining that I live in New York City, a place so expensive that it renders most typical financial standards irrelevant.

As for the instances of PML seen in Rituxan, the actual number is 23 out of a total treated patient population in excess of 500,000, the vast majority of whom were severely immunocompromised lymphoma patients. In that context, the risk of PML works out to .000046% chance of contracting the disease while taking Rituxan. The risk is real, but statistically tiny.

[msladyinca]

Hi Marc,

Rituxan can indeed be prescribed off label for MS. It is in trials for both RRMS and PPMS, but that does not disqualify its use off label for either of those two conditions.

I stand corrected, as indeed it is used off label.

As for the instances of PML seen in Rituxan, the actual number is 23 out of a total treated patient population in excess of 500,000, the vast majority of whom were severely immunocompromised lymphoma patients

According to Medscape alerts, with regard to the two patients that died from PML, the first patient had only six doses of Rituxin, and the second patient had only three doses of Rituxin.

In the small phase II Rituxin study, 104 patients with relapsing-remitting MS were randomly assigned to either placebo or to a single course of Rituxan, delivered in two IV infusions two weeks apart...The proportion of patients who had relapses during the study was 34.3% on the placebo versus 14.5% for patients on Rituxan This difference translated into a 58% reduction in relapses for Rituxan (Note: After 48 weeks, 20 percent of the 69 Rituxan recipients had suffered a relapse...in other words, the drug was not as good at preventing relapses, but was still much better than the 35 patients who received the placebo and had a relapse rate of 40 percent).

The second study, designed to look at the safety of the drug, showed that 26 of 28 people were able to complete the 48-week study, in which they received two infusions of Rituxan two weeks apart and then another course six months later.

Tysabri data from thousands of MS patients treated, showed in clinical trials for all forms of relapsing MS, that there was a 67% reduction in relapses, not 58%.

Additionally, patients who received Rituxan showed a 91 percent relative reduction in lesions vs. patients who received placebo, whereas, the AFFIRM investigators reported that there were 92% fewer gadolinium-enhancing lesions and 83% fewer new or enlarging T2-hyperintensities on MRI in the Tysabri group versus the placebo group.

My main concern is that, based on the new results, doctors may begin using the drug on their MS patients even though it has not been approved for that use. Because Rituxan is not approved by the FDA for use in treating MS, the current study was relatively small and was a Phase II study, which means that it is preliminary but gives reason to proceed with further trials that will be larger and more definitive and more carefully designed to look for potential long-term safety & efficacy data, and as well as adverse events data.

Rituxan is an expensive medication and its lack of FDA approval for MS would likely make insurance coverage or other reimbursement difficult. The lack of Phase III data will also make many physicians reluctant to prescribe it, however, this would be a personal decision and I agree that all choices regarding any medication used to treat our disease should absolutely be a personal decision.

I do hope and pray that the Rituxan studies/trials for PPMS yield great results for many of us, and I hope Marc that you are somehow able to qualify for one of the studies. I believe that it is always good to have a great variety of medications available to us to effectively treat our disease.

All my best,

Lauren

[marcstck]

I believe the phase 3 Rituxan RRMS trial results are due to be released next week at the annual American Academy of Neurology meetings. The PPMS trial results will supposedly be released sometime early this summer.

Thanks for the kind wishes, and right back at you...