Research Study for Tecfidera, Gilenya and Arbagio

[MSW1963]

In April I will have my last Tysabri infusion. 30 days later I will switch to Arbagio.

The DMT switch from Ty to Arbagio is part of a research study of the 3 oral MS meds, Tecfidera, Gilenya and Arbagio. It's to compare effectiveness of the meds, but also because the 2 doc presented the same proposal requesting very close screening of MS patients.

The study consist of monthly 3D-MRIs, blood work to screen for those ineligible for Arbagio and monthly? blood work and MS Neuro office visit, and cost of Arbagio.

There are 2 MS clinics included in the study, Harvard and my MS clinic doc.

I'm real apprehensive about stopping Ty, but my doc's practice is going in another DMT direction it seems.

I would like to hear from anyone who is or will be participating in this study. I assume wer're a small group represented here because of the limited scope of the study.

Anyone else participating in this study?

[bree2013]

MSW1963,

Interesting study. I read you've been on Ty for 2+ years and it's very beneficial to you. I understand your concern about switching. Are you also JCV+ but lower titer? (right term?) Don't remember if that was you or someone else...

The fact you'll be monitored is good -- very good. Now I assume you can change your mind at any time if things don't go as planned? If necessary would the next step be trying Tecfidera or Gilenya?

I hope all goes well for you. Being monitored so closely is a definite plus - Good luck and please keep us posted.

Bree

[MSW1963]

bree2013, yes, just over 2yrs on Ty, my titer was 1.85, more recent one was 1.7?, higher than my MS doc's practice is confortable with. Reading between the lines I think it's more of a liability issue. If things don't work out with Aubagio, I think Gilenya is next on the list for me.

I have no changes on MRIs since I was dx with +20 lesions, with the exception of a rebound type event when I stopped infusions for a few months in the 1st year. I don't expect my MRI status to change with the more frequent imaging, but I am curious never the less.

Also the 3D imaging helps to determine how deep each lesion is, the damage involved, plus more than I know at the moment.

I also think comparisons of the 3 oral meds, plus monthly 3D MRIs, indepth blood work and other screening may add the kind of info doc's haven't had the opportunity to observe in MS patients before now.

It's this package of requirements that my doc and the other MS center doc both proposed for the study, and is the most appealing aspect to me about changing DMTs.

Otherwise I'd stick with Ty, the devil I know, and the only DMT that's offered relief from my wish list of 3 ms sx's. I think I'm developing a case of 'changing dmt cold feet, not to be confused with my usual cold feet.

[Myoak]

Hi Bree and MSW1963,

Hope you don’t mind me jumping in here with a point or two.

First let me say I hope the Aubagio works spectacularly well. There are reasons why your neuro thought it was appropriate so give it a fair chance to work. But if it doesn’t, I believe there are reasons to think Gilenya would, especially if you were having success on Tysabri.

Why? Because some puzzle pieces fit together as follows:

Tysabri hinders B lymphocytes from crossing the blood brain barrier.

Gilyena sequesters these problem B cells in the lymph system.

Pender’s successful MS treatment in Australia was accomplished by enhancing the ability of T cells to clear B lymphocytes (he did this by removing blood from a patient and exposing it to an EBV vaccine; that exposure improved the function of cytotoxic T cells and they killed infected B cells when the patient got the blood back). The patient improved considerably. The links are in another thread.

The drug Rituximab (rituxan) binds to CD20 molecules on B cells and kills the B cells. Rituximab is tremendously effective in MS, comparable to Tysabri in trials. Since stem cells and plasma cells lack CD20 Rituximab does not affect those cells. Because it is coming off patent there is little research with this drug, however, it is being rebranded as Ocrelizumab and that drug is in MS trial presently. The point right now is that it kills selected B cells and is very effective in MS.

Then we have a case published yesterday by MedPage Today (I posted about it in the Charcot Project thread) where a HIV patient who also had MS saw improvement when he was given antivirals “Within months of commencing HAART, all MS symptoms gradually improved. Within 2 years, his urinary incontinence was controlled to the extent that he stopped wearing pads and fecal incontinence resolved. He has had no MS relapses."

Viruses infect and hide in B cells. With the HIV patient when infected B cells were killed by antivirals, the HIV patient saw improvement.

MS shows improvement when Rituximab kills B cells.

MS shows improvement when B cells are killed by enhanced T cells (Pender in Australia).

MS shows improvement when B cells can’t get into the brain because Tysabri doesn’t allow them to cross the BBB.

MS shows improvement when B cells are kept sequestered in the lymph system by Gilenya.

That is why Gilenya may work well for those who have had success on Tysabri. Because both meds deal with problem B cells just in different ways.

Lastly, it is important to begin Gilenya as soon as possible after Tysabri (30 days would be ideal). Why? Because Tysabri is still keeping infected B cells out of the brain and Gilenya takes some time before it works to keep B cells in the lymph system.

The longer the washout period, the greater the probability of MS rebound and the hell that brings. If your MS has been kept in check by keeping B lymphocytes out of the brain why give them opportunity to get in there?

Typically, MS rebound happens 10-12 weeks after stopping Tysabri, if it is going to happen. So begin whatever treatment you choose to follow Tysabri promptly, even if you have to argue with your doctor.

Advancing treatment could maintain coverage effectively enough to possibly prevent a flare-up, IMO. And, the exacerbations following Tysabri discontinuance often seem particularly bad.

I believe I can furnish scientific studies to back-up the statements made here if you have questions. Sorry about the length. Bottom line... if Tysabri worked for you there is a good chance Gilenya would too, based on how they appear to work.

[MSW1963]

Myoak, your insight and generosity is always appreciated. It's restored just a bit of confidence in my decision to try Aubagio.

I'm extremely interested in the study, primarily because it will include comparison of the 3 new oral meds. And I have to admit, the monthly 3D MRIs have a certain amout of 'bling' factor associated with it.

My confidence in the study hinges on my confidence in my doc, and what was not said concerning the MS practice's decision to abandon Ty. The infusion center that once buzzed with Ty patients, nurses and new equipment resembels a ghost town for the past 2 months.

Thanks again for your help

[pennstater]

MSW,

I am still on Ty. my neuro told me that following the AAN meeting, if I needed to go off Ty at some point, he would recommend Aubagio. We had the discussion since 24th infusion coming up, but since JCV-, no change other than more frequent JCV testing.

I hope all goes well for you. Will be following your posts. Good luck!

[Temagami]

Just did some googling and I could only find that Gilenya sequesters T, not B cells. Can you send me a link to a source that mentions the B cells?