My neuro told me today, the number of PML cases is 40 or more. One of the main stockholders resigned and sold his shares. ??? And the current number of patients has not even neared the original projected number. (They consider anyone who tries it even once to be included in that number, even if they no longer take it.)

I'm doing well on Copaxone and will stay on this. I hope all is going well with my friends who are still taking Tysabri (or considering it.)

My checkup today went well and at three months on Copaxone, I'll be sticking with this.

Well, I had infusion #20 on Monday. I am now on the every 8 weeks schedule to minimize UTI's. This infusion was great: no flu like side effects. Sometimes it is really crummy for 2 days afterward and sometimes it is a breeze. Unfortunately, I think I got another UTI that started today. Ugh. So now I have to head back to the urologist.

Last week I finally saw my new neurologist who used to be at Johns Hopkins--basically my MS clinic "stole him away!" I like him MUCH better than the last one who was a dud. We talked about several things. 1. I shouldn't really take a prophylactic antibiotic for a week each time I get an infusion because it may build up resistance to the bacteria and then the only thing that would work would be IV antibiotics. 2. He also questioned whether I should stay on Tysabri--he said it is a little bit of an overkill since I have such mild MS (just the hardly noticeable optic neuritis, a little dizziness and cognitive stuff at that first event). I haven't had a relapse since I was diagnosed 2 1/2 years ago. Now he knows I went on Tysabri because I couldn't tolerate interferons or copaxone and he understands. He also said that we can't know if the Tysabri is what has prevented me from having any more relapses. I told him I was worried about my initial MRI with the black holes. He reminded me though that MRI doesn't necessarily correlate with symptoms. But given the UTI's and the PML risk with such a mild case of MS he suggested switching to something else. It's sad because I love my Tysabri!

He tried to steer me toward Avonex. I had tried Rebif. He thought maybe once a week might be tolerable. Of course I can't stomach that idea!! He also said I could take a steroid pill called decadron on the day of the Avonex shot and that pretty much wipes all the side effects out. But again, the thought of taking regular steroids, even if one day a week, does not appeal to me.

We talked about the pills about to come out--cladribine and fingolimod. Out of the two he would lean toward fingolimod. He is very worried about the cancer risk with cladribine, and not just skin cancers, therefore he wouldn't advocate using that. Of course he said both drugs are serious immune suppressors. It's the same old dilemma: the better the benefit the higher the risk of opportunistic infections.

Anyhow, he wasn't pushing aggressively, just noting different options. We decided that I will get two more Tysabri infusions -- in May and in July. We will then meet in July to decide what to do. He will look at MRI results then. He is hoping that fingolimod may be on the market by then and I would switch to that.

Oh, in the meantime I found out I am iron deficient! I have been taking iron supplements for 3 weeks now and I feel like a new person. My hair stopped falling out, my lips are no longer chapped (weird symptom, huh?) AND the best part is I have stopped taking long naps. I have super energy now--I don't feel sleepy or fatigued like I used to. Sometimes at the end of the day I would just collapse with exhaustion. But now I have much more stamina. My brain feels a lot clearer and my memory is better. I am very happy about all of this! I thought maybe the fatigue was the MS or a Tysabri side effect. Really, it's likely I was very anemic.

Anyhow, I don't mean to go on and on and on and on.....

There is a new article out that breaks down all of the details of the first 28 patients who got PML while on Tysabri. It is excellent. It tells you things like age of patient, gender, what drugs they took before Tysabri, duration of symptoms before PML was diagnosed, symptoms experienced with PML, whether there were enhancing lesions, duration of first treatment of PML to first symptom of IRIS, symptoms experienced during IRIS, JC viral load in spinal fluid, and status of person at last followup. The article offers many suggestions for trials to be done or further questions to be answered. Interesting facts include 1. 40% of people with PML had enhancing lesions 2. several people had seizures so add that to the list of possible PML symptoms 3. PLEX was used for treatment in all but one case. 4. treatment for IRIS persisted for several months in many cases 5. brain location of lesions is more relevant to prognosis than size of lesions. 6. the survival rate is 71%. 7. 54% received mefloquine and 39% received mirtazapine as adjunctive treatment along with PLEX and steroids. 8. 3 out of the 28 were treatment naive before Tysabri 9. 7 out of the 8 deaths were in the USA

"Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases," The Lancet Neurology, Volume 9, Issue 4, Pages 425 - 437, April 2010

Here is the abstract:

Background Treatment of multiple sclerosis with natalizumab is complicated by rare occurrence of progressive
multifocal leukoencephalopathy (PML). Between July, 2006, and November, 2009, there were 28 cases of confi rmed
PML in patients with multiple sclerosis treated with natalizumab. Assessment of these clinical cases will help to
inform future therapeutic judgments and improve the outcomes for patients.
Recent developments The risk of PML increases with duration of exposure to natalizumab over the fi rst 3 years of
treatment. No new cases occurred during the fi rst two years of natalizumab marketing but, by the end of November,
2009, 28 cases had been confi rmed, of which eight were fatal. The median treatment duration to onset of symptoms
was 25 months (range 6–80 months). The presenting symptoms most commonly included changes in cognition,
personality, and motor performance, but several cases had seizures as the fi rst clinical event. Although PML has
developed in patients without any previous use of disease-modifying therapies for multiple sclerosis, previous therapy
with immunosuppressants might increase risk. Clinical diagnosis by use of MRI and detection of JC virus in the CSF
was established in all but one case. Management of PML has routinely used plasma exchange (PLEX) or
immunoabsorption to hasten clearance of natalizumab and shorten the period in which natalizumab remains active
(usually several months). Exacerbation of symptoms and enlargement of lesions on MRI have occurred within a few
days to a few weeks after PLEX, indicative of immune reconstitution infl ammatory syndrome (IRIS). This syndrome
seems to be more common and more severe in patients with natalizumab-associated PML than it is in patients with
HIV-associated PML.
Where next? Diagnosis of natalizumab-associated PML requires optimised clinical vigilance, reliable and sensitive
PCR testing of the JC virus, and broadened criteria for recognition of PML lesions by use of MRI, including contrast
enhancement. Optimising the management of IRIS reactions will be needed to improve outcomes. Predictive markers
for patients at risk for PML must be sought. It is crucial to monitor the risk incurred during use of natalizumab
beyond 3 years.

I am still waiting for my AZ neuro to get the info on pml. Mostly I want to know how many people are on Tysabri 3+ yrs and how many have developed pml in this time frame. I really want this info U.S. only.
Has anybody gotten this info from there neuro ?
Linda

Sorry, my typo! The study is between Tysabri, Copaxone and Rebif, NOT Betaseron!

Yeah!!!! Just wanted to check in and report that I did not get a UTI with this Tysabri infusion (and no prophylactic antibiotics either!).

I had #44 Mon; same as the 43 before it

Yesterday I spoke with my case manager to get switched back to CO from AZ. He confirmed the 42 pml cases thru 3/10, 15 in the U.S and stated there are 60,000+ users (37,000 U.S.). I then asked how many infusions the 2 newest pml cases had-didn't know and then asked how many people had been on it over 3 yrs didn't know that either. Told him since the risk is higher the longer on it (as Biogen reported) we want to know how many cases of pml over 3 yrs and how many people on it (still on it) since 7/2006.

He did say the FDA still approved the 1/1000 ratio. I want the info like we got it before 7/24/09 and told him so.
Linda
I just read new info on pml cases 41 and 42. One had 30 infusions the other 34.

http://www.businessweek.com/news/201...-update1-.html

Biogen Seeks Test for Brain Disease Linked to MS Drug (Update1)

Thought this paragraph was interesting

“Biogen is looking at other biological signs of PML risk that may be incorporated to improve the test, Sandrock said. In those who test positive, Biogen is testing for markers to further determine which patients are at high risk, Sandrock said. Those markers may include certain genes that increase the risk of a brain infection, or viral mutation that allows JC virus to live in brain tissue.”

Hey K!
I'm looking for an article about Tysabri being tested in SPMS that came out within the last two weeks. I know I had it but my filing system is a bit scattered. Is there any chance you have it at hand?
TIA!

Hi Linda!
Glad to hear that 44 went as well as all your previous infusions!

I can't help with the new cases of PML and the count of infusions right now but will see what I can find out when I see my doc next week.

The last time I saw him he explained the numbers and length like this: There are less people who have had more than 36 infusions than people who have had lesser number of infusions. The cohort is smaller and it cannot be compared to the greater number with less infusions. He said the data does NOT show more people with greater number of infusions coming down with PML at a higher rate than people with lesser number of infusions. He said the data actually shows that the rate seems to be trending down rather than up after 36 infusions.

He cautioned that since there is NOT a lot of data available since the number of people in our group is smaller, that the rate may change, but it is not being seen at this point. I believe that the last count I saw for people at 36-48 infusions was around 6400 people worldwide. If someone went out on a drug holiday, they restart at 1, so they are disqualified from the group. He said a drug holiday is considered as missing more than three infusions in a row, but that there are people like me, who missed one infusion or were late on an infusion due to some other reason than actually choosing drug holiday, that mess up the numbers too, but still get counted as being in a group. He also said there are people like Natalie, who are extending the time between infusions, but still receiving infusions, who are counted as being part of a group despite their changed schedule and that changes the group data, or who move from one group to another after being on a changed schedule for a longer time, due to the number of infusions missed despite being on Tysabri for a certain number of years

He said it is getting more confusing as time goes by and the numbers of people on Tysabri go up and that since he is not a statistician, he can't keep track either, but that some poor bugger at Biogen is keeping track of it all with a computer modeling system.

Biogen received a letter from the FDA just the other day, citing them for a webcast that didn't give enough detail/info/bad news about PML. According to Biogen, this webcast was for health professionals only and NOT for general population, and they can not control who releases the info to the general public. This may shut off some of the information that we, as searchers for info, have been getting from outside of "approved sources for patients" As usual, only time will tell.

As an aside, there is still Alex's site for info but it almost seems like maybe the info train is slowing for him also: http://chefarztfrau.de/?page_id=716

One thing I found as strange on his site was post # 40! It's what appears to be a sale of Tysabri on ebay/de ! Click on his one line comment and it takes you to the supposed page!

It's my sincere hope that the work being done on assays and biomarkers will help to clarify risks in the future, for all of us!