This Is MS Multiple Sclerosis Community: Knowledge & Support

[ewizabeth]

Hi Everybody,

I'm thinking about Tysabri, see my doctor on 04/18. I'm eligible for it, checked yesterday with my insurance company. According to them, they could have it set up and sent out to my doctor in 3 business days!

I know the history of T, and my drug history... my tentative plan is, if it works, then take it for 1-2 years until we have the next super-duper drug available with less known bad side effects. Preferably a pill.

I was hoping my doctor would be in the FTY 720 study but I don't think he is. That would be a safe option I think?

I hate decisions like this, I've been weighing this heavily for a long time. But I feel fortunate that I have this as an option anyway. Our insurance has been a blessing.

[HarryZ]

Ewizabeth,

It's always difficult to try and figure out just what drug to take for you MS. One usually looks at how others have done on a particular medication but with MS, the varied results are all over the map and it's almost impossible to determine what the right choice may be.

Do the research (which you have done with Tysabri)look at all the pros and cons, discuss them with your doc and then make your decision. You really can't do more than that.

Harry

[ewizabeth]

Thanks Harry,

I'm relieved to see your reply. I understand your mixed feelings about Tysabri and the company that makes it because I have them myself. I have done lots of research, so I think this is what I'll do unless the doctor gives me good reason not to.

[renrank]

Ewizabeth,

Making a decision regarding starting Tysabri is not easy to do. I just had #5 a week ago, and I am doing great on it. I actually started a thread titled "I love Tysabri!" For me, I had to weigh out whether or not the risk was worth the reward. It is very important to me to be able to have good quality of life, and I would sacrifice quantity for it, but I am really not afraid of PML. The lifestyle was very important to me as well. I am no longer reminded every other day that I have MS, thanks to self injections! I love the freedom of the monthly infusion. I am very comfortable with my neuroligical team... I see an MS neurologist, and his whole team is completely specialized in MS. They monitor all Ty patients very carefully, and you also must be very aware of your own body. I have improved so much... I was having an exacerbation that began somewhere in late September, and I was even on disability from October until February. My neurologist said, "Tysabri doesn't make you better but I swear you're getting better!!" It has been a wonderful change for me, and I would choose it again and again.

I hope you'll keep us posted as to what your decision is regarding Ty. Good luck with whatever you choose!

[CureOrBust]

I was hoping my doctor would be in the FTY 720 study but I don't think he is. That would be a safe option I think?

Your own neuro doesn't need to be integral in the trial. You could find out who is, and contact the recruiting person; http://www.clinicaltrials.gov/ct/search;?term=fty720+multiple+sclerosis Most of these would have a phone number and/or email (Although I just emailed the one in australia, and it bounced, so i'll try the phone number next week)

[ewizabeth]

I have improved so much... I was having an exacerbation that began somewhere in late September, and I was even on disability from October until February. My neurologist said, "Tysabri doesn't make you better but I swear you're getting better!!" It has been a wonderful change for me, and I would choose it again and again.

I hope you'll keep us posted as to what your decision is regarding Ty. Good luck with whatever you choose!

Hi Renrank,

I'm so glad you're doing well on Tysabri. If I decide to take it after seeing my doctor I'll be sure to let you all know. I have some other possibilities at the back of my mind too, but I don't know how those would work out. It's less than two weeks until my appt. now, and maybe I'll know what to do then.

[ewizabeth]

I was hoping my doctor would be in the FTY 720 study but I don't think he is. That would be a safe option I think?

Your own neuro doesn't need to be integral in the trial. You could find out who is, and contact the recruiting person; http://www.clinicaltrials.gov/ct/search;?term=fty720+multiple+sclerosis Most of these would have a phone number and/or email (Although I just emailed the one in australia, and it bounced, so i'll try the phone number next week)

Hi Cure,

I already called the two that are closest to me, and neither one returned my calls. It could be that they already have their quota of patients for
FTY720, I have a feeling it's going to be a pretty popular trial to be taking part in. It has very small set of exclusion criteria and it's a pill!

[rolled]

Ewizabeth, FTY-720 is has more restrictive entry criteria than any proposed first line MS treatment that I have seen tested over the past 12 years. The reason is that its side effects are significant and harsh. Heart and liver especially a concern, but the large immune suppression issues are far greater than with Tysabri. IMO this is a drug that perhaps could be used in healthy patients (other than MS) that are refractory to Tysabri, but prior to using one of the chemo drugs like novantrone.

You can see some of the entry criteria and the nci clintrials database site. As I understand it, many neurologists are extremely reluctant to suggest patients enter this trial as the side effects are substantial, the efficacy is not as good as Tysabri, and half the patients will not receive treatment for 2-3 years. The Long Island primary trial clinic had not, as I understand it, accrued a single patient as of the end of February.

Note the following and the 12% v. 1% incidence of significantly higher ALT levels (indicative of heart and liver damage):

http://www.ncbi.nlm.nih.gov/entrez/quer ... s=16971719
N Engl J Med. 2006 Sep 14;355(11):1088-91.

Adverse events included nasopharyngitis, dyspnea, headache, diarrhea, and nausea. Clinically asymptomatic elevations of alanine aminotransferase [ALT] levels were more frequent with fingolimod (10 to 12%, vs. 1% in the placebo group). One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group.

Fingolimod was also associated with an initial reduction in the heart rate and a modest decrease in the forced expiratory volume in 1 second.

Here is another abstract describing the method of action and cardiac issues associated with FTY-720:

Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.

Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N, Rosen H.

Department of Immunology, The Center for Mass Spectrometry, The Scripps Research Institute, La Jolla, California 92037, USA.

Sphingosine 1-phosphate (S1P) influences heart rate, coronary artery caliber, endothelial integrity, and lymphocyte recirculation through five related high affinity G-protein-coupled receptors. Inhibition of lymphocyte recirculation by non-selective S1P receptor agonists produces clinical immunosuppression preventing transplant rejection but is associated with transient bradycardia. Understanding the contribution of individual receptors has been limited by the embryonic lethality of the S1P(1) knock-out and the unavailability of selective agonists or antagonists. A potent, S1P(1)-receptor selective agonist structurally unrelated to S1P was found to activate multiple signals triggered by S1P, including guanosine 5'-3-O-(thio)triphosphate binding, calcium flux, Akt and ERK1/2 phosphorylation, and stimulation of migration of S1P(1)- but not S1P(3)-expressing cells in vitro. The agonist also alters lymphocyte trafficking in vivo. Use of selective agonism together with deletant mice lacking S1P(3) receptor reveals that agonism of S1P(1) receptor alone is sufficient to control lymphocyte recirculation. Moreover, S1P(1) receptor agonist plasma levels are causally associated with induction and maintenance of lymphopenia. S1P(3), and not S1P(1), is directly implicated in sinus bradycardia. The sustained bradycardia induced by S1P receptor non-selective immunosuppressive agonists in wild-type mice is abolished in S1P(3)-/- mice, whereas S1P(1)-selective agonist does not produce bradycardia. Separation of receptor subtype usage for control of lymphocyte recirculation and heart rate may allow the identification of selective immunosuppressive S1P(1) receptor agonists with an enhanced therapeutic window. S1P(1)-selective agonists will be of broad utility in understanding cell functions in vitro, and vascular physiology in vivo, and the success of the chemical approach for S1P(1) suggests that selective tools for the resolution of function across this broad lipid receptor family are now possible.

[dignan]

Ewizabeth, I was just poking around and don't know if you done this already, but Novartis has a little web screening system to see if you would qualify for the FTY720 trial. Maybe everybody does this for their clinical trials, but I just happened to notice this one.

http://www.novartisclinicaltrials.com/w ... reening.do

[ewizabeth]

Hi Rolled,

You aren't my doctor are you? And I don't mean that to sound insulting at all. You sound very smart, but like you are trying to talk me out of something potentially harmful. It reminds me of my doctor.

Thanks Dignan,

I did see that before. I wished my doctor was taking part but I don't think he is. I don't know that I have the energy to take part in another trial right now anyway. I think I just need to be on treatment. I have some inflammation stuff going on now. I see my doctor on Wednesday. I'll check back in and let you all know what route I take.

I just got a new kitten today, and he's a shy guy! Won't come out of his carrier! He's been in there for five hours!

[rolled]

No way would I try to talk you out of participating in a clinical trial! But, I think if you have not already tried Tysabri then that would be the best course: it has much greater efficacy than FTY-720 and it is safer.

Still, your participation in the trial would be a public service because you would help gather more hard evidence of efficacy and safety.

The purpose of my note was only to correct (not meant condescendingly) what seemed to be erroneous: that inclusion criteria for FTY-720 would welcome a broad swath of volunteers. They want relapsing MS'ers who are otherwise extremely wealthy.

My guess is that they will recruit young, otherwise healthy relapsing MS'ers, emerge with solid efficacy and tolerable safety data, then slap a black box on the medication to limit liability and market the hell out of it. Recruiting very healthy patients is, IMO, the only way Novartis threads the needle on this one: it is really too dangerous (again IMO) to be approved as a first line treatment. With Tysabri on the market already and proving to be safe and very effective, FTY-720 and Novantrone and LDN and Campath should be used only as 2nd and 3rd line treatments.

I do think that FTY-720 will show efficacy that exceeds that of interferons and glatiramer acetate: it works by keeping T cells from your neurons (and from everywhere else!)

If you do choose to participate then you have my best wishes and sincere admiration.

[ewizabeth]

No way would I try to talk you out of participating in a clinical trial! But, I think if you have not already tried Tysabri then that would be the best course: it has much greater efficacy than FTY-720 and it is safer...

... My guess is that they will recruit young, otherwise healthy relapsing MS'ers, emerge with solid efficacy and tolerable safety data, then slap a black box on the medication to limit liability and market the hell out of it. Recruiting very healthy patients is, IMO, the only way Novartis threads the needle on this one: it is really too dangerous (again IMO) to be approved as a first line treatment. With Tysabri on the market already and proving to be safe and very effective, FTY-720 and Novantrone and LDN and Campath should be used only as 2nd and 3rd line treatments.

I do think that FTY-720 will show efficacy that exceeds that of interferons and glatiramer acetate: it works by keeping T cells from your neurons (and from everywhere else!)

If you do choose to participate then you have my best wishes and sincere admiration.

Thanks for the explanation, that is something I can understand. I could translate your first post, but I don't have the patience to do that unless I'm in a classroom or at work. I suppose that part of the reason patients will be interested in FTY720 is that it is a pill; but that does not necessarily mean that it is safer than a shot or an infusion.

I'm leaning toward Tysabri because I'm having some new symptoms now, and I don't think it would be good for my health to go into a trial at this time.

I really appreciate your input though. If what you say about FTY720 is correct, then that could be why my doctor is not participating in that particular trial.

[NHE]

Hi Dignan,

Ewizabeth, I was just poking around and don't know if you done this already, but Novartis has a little web screening system to see if you would qualify for the FTY720 trial. Maybe everybody does this for their clinical trials, but I just happened to notice this one.

http://www.novartisclinicaltrials.com/w ... reening.do

This URL seems to work better...

http://www.novartisclinicaltrials.com/w ... seaseID=78

NHE

[ewizabeth]

Ok, call me indecisive... but I called the neuro's office and requested to be set up for Tysabri today. I spoke to the Tysabri nurse, my doctor is out of town until Friday.

I'm not doing very well lately, with painful spasms that are keeping me from using my arms and back and waking me at night... this has been going on for a few months and it's not getting better, even with two new meds.

With new and worsening symptoms I need to be on a treatment. Wish me luck! I hope I get through the red tape quickly!

[ewizabeth]

Ok, I signed the TOUCH paperwork today. I hope to have my first infusion within a a few weeks. I hope I have very good luck with Tysabri, I need a break!

I explained to the neuro that I wasn't feeling well, and didn't want to participate in the trial I had been waiting for. I just need to be on treatment and need to feel good now (hope that happens!) The infusion nurse said that the patients currently taking Tysabri at their office are staying the same, and not showing any worsening of symptoms.

The neuro mentioned that Campath might be the next up and coming superstar in MS treatments, that it had spectacular results in trials and more trial will resume later this year (I think.) It's a once a year infusion.