The Reason to Get on Therapy and Stay on Therapy

[Lulu54]

This point from today's talk struck me so much that I feel it needs to stand alone.  I hope everyone who thinks they don't need on disese modifying drug therapy will consider these odds.

It has been proven, according to my Neurologist (sorry I didn't write the sources - I will try to get them next time)  that:
50% of Patients who go untreated for MS will develop SPMS in 10-15 years and will need a cane to walk (or maybe more)

34% of patients who go untreated for MS will be bed bound within 30 years of symptom onset.

These are some very sobering numbers.  

be well, be proactive,
Lulu

[fortywhat2]

Thanks for all the input, I have to admit due to cognative issues I don't remember much of what I read so it helps to have others input!  I am currently waiting on test results for Addison's disease... I have to wonder if all these autoimmume diseases that they've discovered I have are tied into my MS and what effects do the medications I take for these other "diseases" effect my MS.  Hummm  always something!  I was also suprised to see more PPMS people... until today I only was aware of Alex sharing PPMS with me.  I appreciate the knowledge and information you've all shared with me.  Although I would prefer things be black and white, with someone saying ok this is going to work if you take it and although there are side effects they are minimual.  Dreams :)

[patientx]

First, I would take with a grain of salt anything Ahston Embry says.  For some reason, he has bone to pick with drug companies, and his essays usually devolve into rants about how bad they are.

As to this essay - first his statement about the confidence intervals in the Veugelers study is incorrect.  When the confidence intervals overlap, this does not necessarily mean the results are not statistically significant. It means you can't say the results are significant based on the CI's alone; further analysis may reveal the data is statistically significant.

As for the NHS study - this study had a number of flaws.  One, is that in order to compare diability progression in people who took DMDs vs. those who didn't, they needed a control group who never took a DMD.  To find this, they used data from Canadian patients.  The problem is, not only were the subjects not age and sex matched, they used records from between 20 and 30 years ago.

An even bigger flaw with the study, in my opinion, is that they applied a "no improvement" rule.  That is, the researchers reasoned that DMDs cannot improve disability in a person, only possibly limit its progression.  So, if over the course of the study, a person actually improved in EDSS score over baseline, he or she was only assigned the baseline score.  If a person was in the midst of a relapse at baseline and showed some deficit (i.e. walking or eyesight), and on subsequent exams did not show this deficit, it didn't matter.  The baseline EDSS was used.  This skewed the DMD data unfavorably. Even one of the authors of the study admitted, that without this no improvement rule, the DMDs did show some benefit in diability progression.

That's not to say the current crop of drugs are perfect, and they leave much to be desired in terms of efficacy.  And, I think everyone agrees (except maybe drug company reps) that they are way overpriced.

[supermum_ms]

Personally I've thought something was wonky with my immune system for over 20 years, long long time before MS ever entered the equation. Interestingly in those years i've been told by many dr's that my immun system was 'over active' or 'over protective' and was unessesarily still attacking long after the initial invader was destroyed. We have noted that i go into bigger relapses 'after' being exposed to infections, whilst the infection is alive and attacking, i feel healthier but once its destroyed its then that i really start going down hill.

If my immune system is awakened it seems to continue to attack, like a canibal eating its self. I've always thought that when my immune system has something real to attack i am better off whilst its distracted, the fun begins when its got nothing 'real' to attack and my immune system already awakened is stuck on being at war. lol

Not scientific but still interesting, my last couple of really bad relapses came after taking the big gun antibiotics, still not sure if it was the type of viral infection or the antibiotics that made everything worse. Its just anacdotal but still interesting.

I would take DMD's, i wouldn't like it but i'd do it because of the way they work and at the moment it's the best option out there. 1% odds in your favour would be a chance worth taking, 30+% sounds good from my perspective!

Cheers.........JJ

[Lulu54]

Bb has this one covered well.  The gilenya does suppress your immune system.  The rest of the DMD's absolutely do not suppress your immune system.

  

[COBOB]

CRABs are NOT immunosuppressants, like IVSM.  They do not suppress the immune system, they modulate the immune system.  That is to say they change the response of parts of the immune system.
In the case of Copaxone, the theory is that it tries to get the immune system used to seeing protein segments that look like myelin.  After about 9 months of therapy, the body changes is response to myelin so that rather than killer T-cells, the body responds with suppressor T-cells and reduces the damage.  

The drug  classes in the arsenal today are: Immunomodulators (CRABs), Immunosuppressants (IVSM, Mitoxantrone) and monoclonal antibodies (Natalizumab, Alemtuzumab, Daclizumab) . I guess Fingolimod would be an immunosuppressant.  It's action is to prevent lymphocytes from leaving the lymph system and entering the blood stream.  

Bob

[JemmAus]

The immune system being surpressed is one reason why I am dubious about starting a DMD. As  single mother, I have virtually no outside help with my child. (Though he is 14!) if he gets sick, there's only me to care for him, so the last thing I want is to catch his diseases then have a relapse as a result.

I often find it ironic that being on a DMD can increase your risk of catching diseases, and those disases can set offf a relapse, yet the DMD is supposed to help stop relapses.....

Mind you, I've only had 4 weeks in 15 months of feeling "normal", so I think I have either gone into SPMS or.............something else....


Oh, and I'm still not 100% sure I ahve MS anyway, and have no desire to inject myself with something if I'm not convinced of the diagnosis.

each to his own, I say!

[Sarahsmom46]

Gilenya, which I am currently taking, is in the test phase for PPMS.  But, like someone has already mentioned it suppresses your immune system and other health issues can creep in.   I just got my blood test results after 6 weeks on it and they are not that great.  But it is a known side effect and you learn to be more cautious about gettin sick. I feel ok and that it is helping, so you have to weigh the good with the bad.

It is definitely worth it for you to ask your doctor about it though.  I wish I could help you find a drug trial for it for your SPMS, but my research abilities are limited and I couldn't pull anything up.  Maybe someone here can find one for you in your area.

I would hope that anyone who has MS will weigh being on a drug versus not being on one will have done their research and talked with their doctor before before they make that decision.  What's right for me may not be right for someone else and I support anyone who choses not to be on a DMD to do so if they made that decision after careful consideration of what the consequences might be.

[HVAC]

My MS Specialist at Duke says Tysabri and Gileyna work better but because they do they suppress the immune system which means more risk. Before the CRABs they use chemotherapy which worked on the MS but had all kinds of issues due to suppressing the immune system.

Statistics like 30% mean nothing the important thing is will it work for you. If you have RRMS you have to choose between trying something and doing nothing.

Beth With PPMS it is individual. Your age and progression plays a part. Gileyna is a start. Not sure if it FDA approved for PPMS yet. There are studies. Many Doctors are hesitant about Gilyena because it is new and they just do not know. They were hesitant about the CRABs years ago for the same reason.

If you look into a drug study and do not like LPs ask. I was about to do one for another PPMS drug, not a DMD, but said not thanks because I do not do well with LPs and you had to have 2.

Alex

[COBOB]

One of the big questions has always been: "Does it work only 30% of the time, or does it work on a specific MS subtype that is about 30% of the total cases of MS?"

Tysabri (a monoclonal antibody) is not one of the CRABs, but can be 70% effective.  Does it cover more disease subtypes?  Interesting since Biogen had a press release today http://www.bloomberg.com/news/2011-04-15/biogen-test-finds-tysabri-patients-with-1-brain-disease-risk.html

Many researchers are beginning to think MS is a set of similar diseases.  Do the DMDs work on some and not other?  Are there specific disease subtypes that respond better to one drug and not others?  Again, an area for more research.

Bob

[maestro1959]

I have Primary Progressive MS.  What is out there for me?  My neurologist has not even brought the subject of medications up since my diagnosis.  Everything I read says there are no accepted treatment for my form of MS.

Should I approach him about meds?  If so, what should I say?  I have no idea.  At present he is only giving me Zanaflex for the spasticity, and my primary care physician has me on Gabapentin.

Thank you for any advice you can give.
Beth

[jensequitur]

It has always bothered me that the rate of success was 30% - I seem to recall that studies can be off as much as 30%, due to sampling ratios and statistics.

I suspect, although I haven't been told this, that I have SPMS.  I really wonder what the point is of taking Betaseron if I won't be helped by them.

[opie74]

I am positive about the future.  With all of the new MS meds getting approved and the ones in th pipeline, we will have to start this research rollercoaster again.  i do think that the newer meds will show a slower rate of progression.  Only time, and a lot of it, will tell!

[HVAC]

For better or worse I have chosen not to be on DMDs for PPMS. They did study the DMDs on PPMS and they did not have good results that is why the FDA did not approve them. This was my personal decision and I know the risk. Others have to make their own decisions. There is nothing wrong with taking a DMD with PPMS. I think each of us has to look at the benefit/risk factor and make our own choices. My first MS Specialist did not want to put me on a DMD in the first place, my second felt I was fine with my decision. Perhaps I will go on Gilyena but I wish it had a been around longer.

If I had RRMS I would be on a DMD even Tysabri.


Alex

[sllowe]

I'm glad to hear you are doing well. I'm with you on the cognitive and memory stuggles - gets hard to keep adapting.

There is a chance the doc was talking about SPMS and the SPECTRIMS study finding.

"The study did not show significant difference in time to disability progression between "either" group. However, there was a significant effect of therapy on exacerbations and other positive treatment-related outcomes became apparent upon analysis."

I think you will find this link more useful for your friends - it's a good summary of multiple large studies: http://www.unitedspinal.org/msscene/2004/09/04/a-summary-of-rebif-clinical-trials/

Like you said, there are a lot of studies out there. And, as Lu alludes too - nothing is 100% but there is hope in the numbers. And, I'm particularly impressed with disease burden results with use of meds vs. placebo. I'm counting on those results, lol

In particular, peek at burden of disease results if you have the chance.
I hope too they discover what works for PPMSers! I have faith it will come!

ttys,
Shell

[fortywhat2]

Hi Shell,
I'm doing well...  cognative and memory issues worsening but I expect that so I just take it for what it is...  As far as the studies for DMD's there are a lot out there... although I don't take DMD because I have PPMS I like to keep up (or try to) for my friends who have RRMS... how are you?  I come on this site and read alot but don't really post ;)  I just thought some might find this benificial.  Sorry for such a long post but it wouldn't allow me to just attach the web address :(   I hope you are doing well!

Hi Lulu'
I'd love to read whatever you get... I try to keep ontop to share with friends :)  and who knows maybe someday someone will come up with meds for PPMS :)
Hope you are well!

Debbie
~Live as if all your dreams came true~

[fortywhat2]

cont.
The clinical trials which tested the drugs and led to their approval were only two years in duration and it was impossible to determine if the drugs had an effect on disability progression over such a short time interval. Instead, the researchers used relapse rate and MRI-detected, lesion development to evaluate drug effectiveness. It was simply assumed these two variables were valid “proxies” for disease progression although the researchers had no hard evidence to support such an assumption.
Notably, subsequent studies have shown that neither of the applied proxy measures correlate to disability progression so it appears that the drugs were approved on erroneous assumptions. Because of these false assumptions, the clinical trial data for the CRABs do not tell us if the drugs have any real effectiveness or if they are no better than proverbial snake oil.
To find out if the CRABs are actually better than snake oil, we must look at the results of the three aforementioned studies which directly examine the question of the effectiveness of the CRABs for slowing the accumulation of disability. The Boggild et al (2009) study compared the disability progression of over 3000 British MS patients who started receiving the CRAB drugs in 2002 versus the established natural progression of untreated patients.
This study was done to determine if the British National Health Service was getting acceptable value for the high cost of the drugs. The main finding of this study is “The outcomes so far obtained in the pre-specified primary analysis suggest a lack of delay in disease progression for all disease modifying treatments”. In fact it was found that “Disease progression was worse than that in the untreated control group” although it must be noted that there was not a statistically significant difference between the two groups.
A recently published study done in Nova Scotia, Canada (Veugelers et al, 2009) looked at the effectiveness of the CRABs on the basis of data from 1752 patients. This was accomplished by examining the time it took to reach disability level EDSS 6 (requires a cane) for both untreated patients and those on one of the CRABs. They found it took untreated persons 14.4 years with a 95% confidence interval of 12-17.4 years whereas the treated patients were estimated to reach EDSS 6 at 18.6 years with a 95% confidence interval of 15.9-21.9 years.
The authors trumpeted these findings as proof the CRABS actually slowed progression but unfortunately they seem to have missed the meaning of confidence intervals for statistical findings. Because the 95% confidence intervals of the two findings overlap, this means there is no real statistical difference between the two results and thus their data really demonstrate  that the drugs have no statistically significant effect on progression.
The third study by Ebers et al (in press) very nicely complements the other two studies in that it compares the current clinical outcomes of the persons who got betaseron during the original betaseron trial done 16 years ago (181 subjects) with the persons who were on placebo in the same trial (79 subjects). The basic finding was “No differences in outcome between original randomization groups could be discerned using standard disability measures”.  
Looking deeper into the data, we see findings such as everyone got to EDSS 6 by about the same time, 12.8 – 16.1 years. This finding is important because these values agree very closely with those of the Veugelers et al study. Also of importance is the finding that 38.6% of untreated patients (those on betaseron for less than 10% of the time) reached EDSS 6 within the past 16 years. This compares with 35.7% of treated patients (those on betaseron for over 80% of the time) reaching EDSS 6 in the same time interval. Once again no significant statistical difference was detected so we can say with some confidence that using betaseron for 16 years will not decrease your chances of declining to EDSS 6 within that time period.
Because the results of any single study can always be questioned, given imperfections in design and data collection, it is important that we now have three independent studies which look at the effectiveness of the CRABs in slightly different ways. Notably, all three studies robustly show that the CRABs have no statistically significant effect on the long term progression of disability.
Given the same result from three different and quite rigorous studies, there now is no reasonable doubt that the CRABs don’t work. Thus we can say the CRABs are really no different than snake oil. I realize this must be somewhat discouraging for many persons with MS who were hoping the drugs would slow their decline. However, at least we now know the drugs do not slow decline and persons with MS can make a rational, science-based decision on their use.
It is also hard to ignore the fact that the neurologists who have been unreservedly prescribing drugs that clearly don’t work are the same ones who now are warning their patients not to address an established, serious pathological problem which is commonly associated with MS - impaired venous drainage from the brain. What makes this even worse is the fact the angioplasty treatment, which can safely and effectively resolve the problem and which has resulted in very obvious, beneficial effects (often spectacular) for almost every one of the 1500+ people who have had it done, is being withheld from persons with MS.
To me, something has gone terribly wrong in how persons with MS are being treated by neurologists. Ineffective drugs are being pushed and a potentially very helpful treatment is being suppressed and denigrated. I suspect when the smoke eventually clears and rationality returns, it will be found that monetary factors rather than health concerns are behind this ugly and unacceptable situation.
References
Boggild M, Palace J, Barton P, Ben-Shlomo Y, Bregenzer T, Dobson C, Gray R.,
Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator. BMJ. 2009, 9 pages.
Ebers, G, Traboulsee A, Li D, et al., Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial.  J Neurol Neurosurg Psychiatry, in press, 6 pages.
Veugelers PJ, Fisk JD, Brown MG, Stadnyk K, Sketris IS, Murray TJ, Bhan V.,
Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation. Mult Scler. 2009 Nov;15(11):1286-94

[fortywhat2]

Hi Guys...
This is one article that a friend provided me with, she see's the same neuro... there are many other.  The study my Neuro told me about I think was done in one of the Boston hospitals...
New Studies Show the MS Drugs Don’t Slow Progressionby DIRECT-MS on Wednesday, October 6, 2010 at 12:24pm
New Studies Show the MS Drugs Don’t Slow Progression
Ashton Embry, July 7, 2010
Five years ago, I wrote a New Pathways column on the value of the commonly used, CRAB drugs (Copaxone, Rebif, Avonex, Betaseron) for MS. It was based on published evaluations by the Cochrane Collaboration, an organization which is free from drug company influence. Based on their objective analyses, my unavoidable conclusion was that “the available data on the effectiveness of the MS drugs indicates that there is very little evidence that the interferons do much good and that there is no evidence at all that Copaxone has any value.”
Not surprisingly, this conclusion did not sit well with many people who were taking the drugs and it was completely ignored (as were the Cochrane analyses) by the neurologists who over the past 5 years have kept prescribing the drugs as fast as they can. The annual revenues from MS drugs is approaching the 10 billion dollar mark, much to the satisfaction of both the drug companies that produce them and the neurologists and MS societies that receive substantial financial and in-kind benefits from those drug companies.
I must note that, in my 2005 article, I did add the caveat “that future proper studies and honest presentations of them may one day show these drugs have some value”. The good news is that we now have three, completely independent studies which look at the value of the CRAB drugs for slowing disability progression over the long term.
I must emphasize that the only true measure of the effectiveness of an MS drug is how well it can slow MS progression. Unfortunately, because MS develops very slowly, it takes years before the effectiveness of a drug can be properly assessed and hence it is only now that we have some good data on whether or not the CRABs are effective or not.

[sllowe]

Hi Fortywhat,

Nice to see you back. I'm very surprised the doctor said this- it's simply untrue. In long and short term studies, (Prisms to name just one where interferon is concerned), the opposite is found over and over  - that the DMDs not only reduce relapses, but additionally MRI burden, and disability progression as compared to placebo.

I only hope there was something lost in translation, and the MS clinic doc did not say this. It's completely opposite of study results.

How have you been making out?
-Shell

[Lulu54]

The point is the odds are already pretty crappy.  No, the DMD's are not 100% but if we can increase the odds in our favor even a bit and make it less than 50% and less than 34%, the point should be considered.

I'll get the references from him at the end of the month when I see him again.

best,
Lulu

[fortywhat2]

Hi Lulu... it's been a long time since I've posted but... this caught my eye!  I go to a neurologist that is part of a multiple sclerosis clinic at Beth Israel Hospital in Boston, MA... she has shard info with me of studies done on MS and DMD's  The bottom line in these studies showed that although DMD cause fewer or less intense flairs each month at the end of one year there is no less progression in the disease of the patients using DMD's vs. those using placibo.  And long term studies back this theory even more.  Just thought I'd share this information with you.  I have friends who have RRMS and have chosen to stop DMD's due to the side effect after reading these studies.  I think if you google the subject you can pull up the info (I haven't done that cause I don't use any DMD's)  

[Lulu54]

Bob is right that it is rx'd here in the US.  I don't know the procedure on how you could push in CA for the same, maybe someone else could help with this question.

I am going to a longer seminar with him on April 30 - I'll post another call for questions closer to that date and please help me to remember to add that to the list.

[COBOB]

A doctor could prescribe a DMD for SPMS, but it would be considered an "off label" use (at least in the US.)  The US FDA approved the DMDs for RRMS.  There are no studies or applications for their use to treat SPMS.  In the US, once a drug is approved for human use by the FDA, doctors can use it for the approved use or for other uses.

I can't speak for what is allowed in other countries.

Bob

[candy158]

Lulu, they still won't give me DMD's, and I do have SPMS ................ would it help to get them, or push for them???  

Just a thought,

Thanks for all your caring,
Candy