Bad week for some of us on DMD’s

[doublevision1]

I appear to be in the same boat as Ess and Gollie, however my problem is with Rebif.  My liver enzymes were up, then down, now up again.  I am apparently in the 3.7% of patients whose liver enzymes elevate on the low dose of this drug.  My neuro has taken me off the meds, for now temporarily but possibly for good.  He wants to monitor my liver enzyme levels until mid-June and then make a decision.  If they are back down, and my condition is stable, he may have me try Rebif again.  If the levels remain above normal, and/or my condition flares again, he will not have me try it again.  

We discussed Copaxone as an alternative.  However, he thinks that Novantrone may be the route to go, at least in the short term.  He describes my disease as ‘very active’ given two relapses in 7 months, and only diagnosed last October.  He says he may not want to spend more time figuring out if Copaxone will work for me, if it turns out Rebif disagrees with me again, meanwhile my disease is very active and doing more damage.

After having a few days to mull this over, I am thinking I should be scrapping Rebif NOW and using this time to try Copaxone, rather than being on NO treatment for the next couple of months.  Either I will find that I tolerate the Copaxone, or I will not and then can try the Novantrone.  I would certainly prefer taking a less aggressive approach initially.  I read a study on Novantrone used on patients with early MS and very active RRMS, and the results are encouraging, although one person developed leukemia which is certainly concerning.  Long term there are cardiac risks so this drug is limited to about 2 years of use.

I discussed all of this with my caseworker at Serono, and she seemed skeptical that I would be successful on Rebif in the long term, given this situation so early in my treatment. I had only been on it for 8 weeks and was only at the low dose (22mcg); never even made it up to 44mcg which is when more patients will typically develop the liver enzyme issue.

So for all these reasons I think I should kiss Rebif goodbye now, and give Copaxone a try, and hope I don’t have the problems that Ess and Gollie have experienced.  It is frustrating that I live so far from my MS clinic.  I am considering emailing my neuro tomorrow stating my concerns and requesting he consider Copaxone now rather than waiting it out with Rebif.

My question to you is…..if you were in my shoes, what do you think you would do?

I would be grateful for your insight on this.

db1

ps to Ess and Gollie: I really hope that you will do well on one of the interferons.  Other than the liver enzyme issue, I had no problem with Rebif as far as other side effects or the injections themselves.  And the liver thing affects so few people, just my dumb luck I guess that I happen to be one of them.

[doublevision1]

Thanks for your replies.  You all raised some very good questions that I will definitely be adding to my list for my neuro.  Very good point about Tysabri...I have already started researching this and will raise this as a possible option for me.

Thanks for your support.  What would I do without this Forum?  Go completely nuts, I suppose...LOL

db

[sllowe]

Hi Db1

I'm sorry that you have to even have to address this.  I was so hoping the liver enzyme would stay a fluke for you.

Since it has not for now, I'm glad to see that your Neuro is going to see what they do when you are off the Rebif.  But, like Doc Q says, sounds like it's the culprit.

My advice too is to talk w/your Dr about Tysabri, that way you are looking at all of your options at once.  Even though your course seems to be progressing at this time, you still have time to weigh things out.  I think you have the protection of the Rebif for about 3 months, albeit at a lesser strength, you still have a little protection while you decide.

Standing here w/you Db,
SL

[Quixotic1]

I just reread your post and I agree that your neuro's concern may be out of proportion to what you are going through.  The double vision is a real problem, but you're not rising higher and higher on the EDSS scale, like I am.  I can see your current desire to stay with a conservative course.

Q

[Quixotic1]

Well, I heard my presence requested and will add what I can.  I do not know a lot about this topic, but know a little about drug reactions in general.

DB1 - I suspect that you are one of the people whose liver is not reacting well.  You did say that you have had elevated LFT's (Liver Fuction Tests) in the past?  If you have a touchy liver, it's likely that the Rebif is setting it off.  They do check LTF's for a reason on everybody taking an Interferon.  But, because our options are so limited, I do understand the thinking of your neuro in wanting to be sure that it is the Rebif causing the problem.

Something as minor as a viral infection that barely makes you sick can elevate liver enzymes, so who knows?  I know that in my whole life I have never had mine high.

So, Copaxone:  I have heard comments by neuros and people here - but have not read anything substantiating it - that Copaxone is not the best choice for aggressive MS.  Beyond that, I don't know.

But, I do want to know why there has been no discussion of Tysabri.  Tysabri and Novantrone have equal risks of a fatal side effect - about 1 in 1000.  The big difference is that Tysabri is not a chemotherapuetic agent, there is no lifetime dosage limit as in Novantrone, and the deaths all occurred while it was being used in conjunction with other hefty meds.  In MS it was with an Interferon.  Most researchers believe it was the dual-whammy of the combination of meds that led to the PML.  That's the main reason it was re-released.  Also, one of the people who died was being treated for a disease other than MS. (I think it was Chron's).

One the other hand, Novantrone is a known chemo and cytotoxic drug which does open you to serious opportunistic infections, possible blood malignancies (lymphoma and leukemia) and to cardiac toxicity.  I believe the cardiac toxicity is cumulative.  You get a little all along, until the major tests start showing it.  Then they stop the med.  You do have some damage.  Don't think it is an all or nothing deal.  You don't just go along with no effects on the heart and then wham you get some.  (I think this is true.  This is how most of those meds work)

I just read a large study on the decreased cardiac function of women post-chemo for breast cancer.  Chemo has bigtime effects.  Cognitive damage (as if we'd notice!), cardiac or pulmonary drop in function. I think the big difference is that Tysabri got all the news and Novantrone is "just chemotherapy."  Lotsa people are on chemo.  

After Novantrone, then what, 2 years later?  I guess it would be the hope that some of these MS drug "on the horizon" would have appeared.  It sounds like Fingolimide will be here.

I recently had opportunity to consider this very question for myself and looked at both drugs.  My choice, for me, would be Tysabri.

Given what I know (precious little on this topic) I would, for myself, avoid cytotoxic (cell-killing) chemo agents with all I have.  I feel bad enough without losing cardiac function and possibly pulmonary function and facing future risk of lymphoma or leukemia.

So, that is my two cents worth, but I couldn't right now defend my remarks with much hard data.

Quix

[gollie]

Hi Db:

Wow this has been a bad week for several of us.  I am so sorry to hear about
the liver enzyme issue. That would scare me more than the burns I got.

I  am relieved to hear your doc
stopped it. My thought on the fact that he wants to try it again after your liver
enzymes go back to normal,  kind of tells me that he wants to be possitive that
it is the rebiff causing it.  (especially since you have had them elevated in the past).
but Im not so sure I would want to have to try the rebiff again, after taking the
time to get your levels back to normal.   (it a tough decision on that one. I would
want to be absolutely sure if  its the Rebiff causing it.)  It is  a lousy way
to have to try and figure it out.  That will have to be your personal decision in the end, not
the docs.

And next off,  If it were me, I believe in all honesty I would wait till my enzymes
were back to normal, and I would give myself at least 6 to 8 weeks to be sure
the rebiff is out of your system. ( Im not sure how long it take to leave your
system after stopping it)

Then I would insist on trying the copaxone.   I understand that we want to get
another DMD as soon as we can, But we need to be safe about it.  I would
seriously want to  be sure it was the rebiff causing the enzyme raise. and also
have it out of my system. even if it did take more than a month.

This way, when you start copaxone, or another type, you will be able to give
it a good fair shake.
I am not sure, how bad off your doing physically, (Im not doing real well right now)
but, even so,  I dont think I would be willing to risk the novantrone just yet. especailly
since its limited, as to how long it can be used for. ( let alone the side affects)
I would be thinking that, wow what if I need it later, if things get real bad for me.
Even tho things are not to great with me right now,  

This is just my opinion on what or how I would handle this. As it is, I am going to
see what my doc say, On the 6th.  I am going to give myself at least 4 weeks
before making a decision on a new DMD.  

I hope all goes well for you, please let us know what you decide.     Gollie

[doublevision1]

Thanks for your post re: Imuran.  I hadn't heard of it and in doing a quick scan I can't find anything that says it is approved in Canada for treating MS but I will keep looking and inquire about this with my neuro.  It looks to be in the same family as Novantrone.  I noticed it can be used in conjuction with ABCR drugs to boost their effect.  That is interesting.

Much appreciated.

db1

[doublevision1]

Yes, drastic indeed!  Till now I hadn't thought of my neuro as a jump-the-gun kind of guy.  This was the dr who wanted me to wait to start my meds until I got accepted into the virtually free provincial MS drug coverage program.  It takes about 4 months for the paperwork to go through (I just got accepted).  I wanted to start Rebif back in December, about 6 weeks after dx.  It took quite a bit of insistence on my part for him to agree to start me before this coverage was in place.  As it turns out because of the back and forth on this, I didn't start until late February.  Despite the fact that I have 90% drug coverage at work, and am very fortunate that finances are not a worry for me, it took a lot of convincing for him to call in my prescription when he did.  I think he thought he was doing me a favour wanting me to have full coverage (he said he wanted to ensure there was no cause for disruption in my treatment), but I was annoyed that this decision was not mine from day one.  Who knows if I had started treatment when I wanted whether this last relapse could have been avoided?  At the very least I would've known that much sooner that my liver wasn't going to tolerate Rebif, so I could get on with something else.  Oh well, I can't back the clock and must move forward.

Anyway to make a long story short on the above anecdote, based on all of that, I didn't think he was a panicky urgent kind of doc.  Things have sure swung 180 degrees from 4 months ago, based on this last relapse.  You are right, it was pretty severe even though it was limited to sensory (and fatigue, keep forgetting to add that since it is such a normal part of life now).  Basically entire left side from shoulder to toes, and very bad burning in my arm and hand which continues despite IV steroids 3 weeks ago.


Re MRI, I am scheduled for a follow up MRI on May 16.  There was something weird at my C7 and from what I can interpret from my report, if it is anything it appears to be non-MS related.  I also asked to ensure that T-spine is imaged at the same time as it was never done, and my first major flare was described as partly thoracic.  So I won't be suprised if they find a lesion/lesions there.  I still have double vision but it is much better than at the start.  Functionally it still impacts me about the same; can't drive, must limit TV, reading and computer, however my measurements have decreased a lot.  No change at my last eye exam so I will wait a while before I have them checked again.  The good news is that neuro says that recovery of normal vision is still possible, he has patients for whom it took over a year.  It is all about the slow process of the affected tissues repairing themselves.  

Your suggestion of getting a second opinion is a good one.  I don't know how fast I could get an appt or even if I can do this on my own without a referral from my GP or neuro.  One nice thing about my neuro is that he does not seem to have that arrogant swagger that many do, and I don't think he would resist referring me if I asked.  I will try the two neuros I happened to see during my diagnostic phase, maybe one of them can see me.  I'm thinking now that I am in the hands of a MS specialist I may not be so lucky to be seen so quickly as I was to see my current neuro.  It is worth a shot though.

Thanks for your comments and suggestions.  

db1

[Heather3418]

My boyfriend long ago, whom has MS, used Imuran, when all the other DMD's failed him.  He has Primary Progressive MS and has declined steadily over the years from what I have heard.  He used alot of Solumderol for relapses which were severe and never truly went into remission.

I hope that I am naming the drug properly.  I do believe it IS called Imuran.

Quix I hope you will jump in on this discussion.  It's a very vital and important discussion as you can see.  

Heather

[essdipity]

Sorry, I misread about your MRIs. Still....

ess

[essdipity]

The Novantrone study is interesting indeed. It does sound drastic though, and very chemo-like. Yikes.

I also would be hesitating, for sure. Most neuros are slow to do anything, but yours might be jumping the gun. I know your vision has been by far your worst symptom and has kept you off work for many months. How is it now? And regarding your relapse, it may have been basically sensory, but it was pretty bad, wasn't it? How's that part now?

I really don't remember when you had your last MRIs, but were they the 3-T variety? If not, I'd be pressing for that at this point. The more info the better since major decisions are underway, or soon anyway. And is there a way to get a quick consult with another neuro? I'd press for that too. This is so important.

Please keep filling us in.

ess

[doublevision1]

Mainly what I know about Novantrone I have gleaned from reading a study done in Italy and published in 2007 entitled: "Mitoxantrone treatment in patients with early RRMS."  

It describes this drug as a "strong immunosuppressant agent" - basically a form of chemo - for use in patients with "worsening RRMS" as well as secondary progressive and progressive-relapsing.    It is used as "rescue therapy when immunomodulatory drugs have failed, and in patients with aggressive disease or a large burden of disease activity."

In this small study (45 patients), at the end of treatment, 53% of patients had no increase in active T2 lesions, and 73% showed no increase in new T1 lesions.  At follow up, 91% showed a stable MRI pattern with no active lesions.  More than half were relapse-free, 3.6 years after treatment. There was also a significant reduction in EDSS scores.

Very uncommon but serious possible adverse events are cardiotoxicity, and leukemia (one case in this study).  Cardiac function is monitored and treatment stopped if there are problems.  Treatment is delivered by infusion every 3 months, and is limited to 2 years I think.  Less serious side effects include nausea, vomiting, hair loss, although I have read that the dose is lower than for cancer treatment so many people do not experience these side effects.  

The fact I am even being considered for this drug concerns me in terms of the implications of the status of my disease, which apparently is worse than I realized.  I'm a bit surprised by my neuro's impressions, as I have heard of others who have had more than one relapse in a year and are on one of the ABCR drugs.  My symptoms are mainly sensory - numbness, dysthesia, plus fatigue and double vision.  No mobility, cognitive, vertigo, incontinence problems whatsoever.  So far only two lesions have been detected on my MRI, with 'subtle white matter changes' on my last one done in March.  I wouldn't have considered all of this to be a huge concern but the timing of this recent relapse seems to have my neuro very concerned about my prognosis.

Since I wasn't even on Rebif long enough to know whether it would positively impact my disease, I'm a bit surprised that my neuro would be so fast to move towards this aggressive treatment when I haven't even tried Copaxone as an alternative.  I hope I can talk my neuro into taking this approach first.

To answer your question Ess, I do not have allergies although tend to have sensitive skin, however this problem is not severe.  I had no problems with my Rebif injections beyond mild redness.  No pain, swelling, itching, etc.  What your doctor said about being predisposed towards a rise in liver enzymes is interesting.  I don't believe I ever had this problem other than some elevation when I had mono 19 years ago.  Perhaps that set me up for failure today?  Who knows.....


db1

[essdipity]

Hi!  I'm so sorry this has happened to you. It's a tough proposition and I'm thinking there are no good answers. I'm sure you know more about Novantrone than I do. Is it infused? Is it one of those for which there is a max lifetime dose? Aside from leukemia (dear God), what are the usual known side effects? In your shoes I would read up as much as possible on this, as soon as possible.

It does sound as if Rebif is not for you, and if I were you I would not consider going back on it, liver or no liver, because it isn't helping, so why waste time. So that would leave Novantrone or Copaxone without waiting. Do you think you could talk your neuro into Copaxone at this point? Do you have sensitive skin or any allergies? Copaxone, though, has not been shown to be better than an interferon for MS overall. As far as I can tell it's mainly a question of what you can tolerate.

Regarding liver function, when discussing Avonex I asked my neuro about this, and he said point blank that Avonex will not cause a rise in enzymes if you don't already have a tendency towards that. That sounds too broad to me.

Anyway, I hope others here, including knowledgeable Quix, will give you their always good advice.

ess