Most neurologists recommend a DMD (disease modifiing drug) , as soon as there is enough evidence to dx CIS (clinical isolated syndrome) or MS.
DMD are about 29% effective in reducing relaspes.
I was dx earlier this year, and at this point, I have decided against a DMD. I am on a drug that is used off-label for treatment of cancer, MS and other diseases. It is call LDN (low dose naltrexone). It is said to work by modulating the immune system. It is not popular by most medical persons, but my Neuro was open to let me try it.
I got dx'd in September of this year and my neuro hasn't started me on the meds yet. I do know that the earlier you start the meds the better chance you have of them working long term with reducing relapses and disability.
I do think that it is also a personal choice. I am being treated for my sx right now.
There is a link to MS and genetics, there is more of a chance to get MS if you have a family member dx'd with it.
DMDs are designed to prevent the attacks. DMDs are very expensive compared to the cost of Methylprednisolone (IVSM also called IV SoluMedrol) used during an attack. Studies have shown that people on DMDs have a lower disability score at 10 years out than those not taking DMDs. I have been taking Copaxone (one of the DMDs) for a couple of weeks now.
There is some evidence that a certain HLA gene sequence predisposes some people to MS. Not everyone with the with the sequence gets MS, The incidence of MS is about 1 in 750. If you have a sibling with MS it jumps to about 1 in 400. This makes it look like there is some genetic relationship, but it is not something that is solely genetic (which would be something like 1 in 4.)
LDN has reports of extreme success in reducing disease progression as well as relapses. Here is a link to that information.....and if you google LDN and MS, you will get a great deal of information.
I agree that there needs to be a large double blind study on LDN, but until then, it is hard to dispute the reports given by MS patients taking LDN. Here is another very informative site of actual MS patients and their comments and discussion on LDN for MS.
Actually, Methylprednisolone stop the infiltration of WBCs and stops the vascular wall inflammation. It also effects the inflammation of brain tissue. You see t as treating symptoms, but it directly stops the assault. It doesn't prevent or slow disease progression, but it performs that same function as a DMD is an acute attack. It is first and foremost an Immunomodulator. It temporarily and directly stops the assault. DMDs try to prevent the attack, If you are on DMDs and have an attack, the next treatment is IVSM.
It doesn't treat the symptoms. It treats the cause of the symptoms.
I was very interested about the methylpredisolone, Sorry to change the subject lol.
My neuro started me on methylpredisolone 4mg yesterday, He said that it isnt a major dose but he wants to start me on something......I woke up this morning and already feel better not complete like before and I dont know if it could work that fast or not but either way its nice to really feel clear and not flat, Im walking better and and balance better. anyways just wanted to say intersesting to see that they use that for ms.This is the second time I started to feel better and got knocked back on my a&& this time I pray it holds :D
The MS Pluse dose of methylprednisolone is 1000mg (1 Gram) in 100ml of saline once a day IV over one hour for 3-5 days. Oral doses on the 500-1000mg range have been shown to be effective in immunomodulation and in the control of inflamation (inflammation). Small doses like you are taking are used to provide a small degree of immunomodualtion when taken over a longer period of time (like a SoluMedrol Dose Pack.)
Right, Bob. It does stop the assault but it has a different role in treating our MS than the DMD's; it appears we are discussing this with different semantics but on the page. If only it were so simple that prednisone could keep us free from attack, we would all be on regular therapy all the time. DMDs and the steroids both serve a different function in treating our MS - I'm glad both are available.
Surth - sorry that your thread has been highjacked with all these other discussions. We sometimes get off track with comments here and there. I hope you have found your answer in all of this chat. If not, please let us know and we'll try to keep it to the point.
Actually, steroids might be able to hold off the attacks, if we could take them long term. The side effects would be worse than the MS, That's really the issue. Both corticosteroids and DMDs are immunomodulators. DMDs seem to be better tolerated for long term use. Copaxone and Steroids also seem to have an anti-inflammatory effect.
As far as the original question, no one has to go on IVSM, but it reduces the damage and can stop an attack. DMDs are taken to prevent the attack. It's that old thing about an ounce of prevention being worth more than ....
states the following about Steroids for MS Relapses:
While glucocorticoids are certainly effective at reducing the immediate impact of relapses, they have been found to have no effect at all on the overall progress of the disease. I would like to reiterate this: steroid use does nothing at all to delay the progression of multiple sclerosis. Seen this way their use is merely palliative much as taking an aspirin to treat a headache reduces the pain but does nothing to address the cause. This would be fine if steroids didn't have such significant side-effects.
I believe daisy.girl has provided us with the correct passage from the quoted site. She is correct in that steroids are merely palliative and do NOTHING to prevent disease progression. They shorten the amount of time one has the symptoms.
For instance, with someone with optic neuritis. The steroids help shorten the time one experiences the pain and vision limitations. Eventually, even WITHOUT the steroids, one would still be left with the same residual side effects with or not the steroids were used.
DMDs are used to SLOW the progression of the disease but at this time the ones available to us for use average only about a 30% success rate at slowing/stopping the progression. I believe there have been studies that even without total success (stopping progression) that there are documented studies to prove that it does increase the time one is functional and able to perform their normal activities, even with help. I'll return with documentation to support this last statement and ascertain if my understanding was correct.
One thing they fail to address in that study my friend is quality of life. Without steroid treatments, I don't even want to guess where I would be. I can tell you, I couldn't hold my head up or care for myself. I guess I would take steroids along with the risks to have some kind of life.
I have 3 friends who are not on dmd's. The one has been on everything under the sun and just had a major allergic reaction to copaxone about a month ago after being on it for 15 years. She told me she is not going to use another dmd for quite a while. She told me she actually feels better. The other 2 use diet, and natural supplementation to combat it. Does it work? I don't know. Although MS is a desease, we each have to figure out what we are personally comfortable with doing as far as treatments, etc. We can toss various treatments around and one person may swear by it, while another says, "no way will I try it". It is an individual desease with no set pattern. I am using copaxone (sometimes) and was using it consistantly and still had an exacerbation. I've only backed off since I realized it was causing major insomnia. I'm not giving up on it, yet.
All of these medications have been shown to reduce the
frequency of MS relapses and the development of new lesions.
In individual clinical trials comparing a drug versus an inactive
placebo treatment, MS attacks were reduced by 28–68 percent
by different agents. In the clinical trials, most people were also
found to have fewer, smaller, or no new lesions developing
within their central nervous system as visible in MRI scans.
Preventing permanent damage
Permanent damage to nerve fibers (called axons) occurs
early in MS in association with the destruction of myelin.
Overall brain shrinkage (or atrophy), can occur early in the
disease, and damage can be ongoing even when the person
has no symptoms of an attack and feels well. Therefore, MS
specialists advise the early use of a medication that effectively
limits lesion formation and brain atrophy, or shrinkage. In
the opinion of the National MS Society’s Clinical Advisory
Board, limiting lesions may be a key to reducing future
permanent disability for many people with MS.
None of these medications is recommended for women
who are pregnant or plan to become pregnant. Physicians
should be consulted. Most women will be advised to avoid
using these medications during pregnancy."
This but an excerpt that I found in a great source, the National Multiple Sclerosis Society Foundation website. It discusses each of the DMD, including the newly released pill / Gilenya, in some degree but does not cover all possibilities.
Hopefully, this will help to clear up any misconceptions about their use.
Good information Ren.....
The ABCR meds are the ones 28-30 percent effective, and only Ty makes it to the 68%. And I believe a recent study has shown that there is actually around 50% of MS patients that do not repond at all to any DMD.
It really makes it difficult for us patients to know what to do, it is so frustrating!
While looking for this data, I came across these very disturbing studies:
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.
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.
To find out if the CRABSs are actually effective, we will look at the results of the three recent 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 prespecified
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.
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.
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
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.
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
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
show that the CRABs have no statistically significant effect on
the long term progression of disability.
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.
The study strongly suggests that there are two major types of MS and that a simple blood test can tell one from the other. By itself, that would be a major finding. But that's not all.
One type of MS responds to beta interferon, generally considered the best treatment. The other type does not -- and beta interferon treatment may even make it worse, find Stanford University researcher Lawrence Steinman, MD, and colleagues.
Not sure they are front runners, but they are they best we have today. For a large cohort, they will overall have a better outcome on DMDs while treating flairs with an IV steroid. One of the problems is that many people miss flairs and the opportunity to stop that damage in its tracks with IVSM. So just taking a DMD is really not good enough. You have to treat flairs. One flair on an optic nerve can leave you blind.
IVSM has direct anti-inflammatory and immunologic effects on the body. It doesn't stop paralysis or paresthesias. It suppresses parts of the immune system. Hardy just treating a symptom. It stops the demyelination and reduces the inflammation. Those effects stops the paralysis or paresthesias. Dexamethasone can also be used. It is so powerful as an anti-inflammatory, it is used to treat cerebral edema and altitude sickness. I don't think I would call them palliative.
To be fair, I take Copaxone. I know more about it than the other DMDs. I know it is 4 amino acids found in myelin that make various combinations of protein segments designed to be a "false target" for the immune system. That being said, it was designed to work against EAE, not MS. TEVA got lucky. It takes 6-9 months to become effective. I have also been treated with IVSM.
I try to pick words carefully, but sometimes my MS brain misses something,
What I have read and been told by Neurologist is that once we experience symptoms of a relapse, the entire damage has already been done. It may take a while for the full extent of the damage to reveal itself. The steroids only help you to feel better. The steroids have no effect at all on the overall progress of the disease
I guess the opinion is different between Neurologist and Neuro-ophthalmologists. Mine indicate that since the damage to the BBB goes on for about 40 days as indicated by MRI studies, they fell that relapses should be treated. Since most of my symptoms seem to involve cranial nerves maybe that is reasonable.
There are a lot of opinions, I have a tendency to go with my docs. I deal with my MS center and they have one of the top docs in the US, They were supportive of Copaxone. They felt it was the best choice for me, They tell me to treat attacks because the vascular leakage appears to last about 40 days,
You know, if all the data was in on MS, we would not be having this discussion or trying to figure out if MS was multiple diseases or not. I will side with taking my Copaxone and IVSM at the first sign of an attack, No sense waiting and letting more damage occur or if your guys are right, no sense being in pain/discomfort.
This is a great discussion of the roles of the 5 major drugs used to treat/palliate our MS and relapses. I am interested in the studies that are showing that by about a 1 1/2 decades there is little difference between treated and untreated. I do think we are missing something though even in those studies.
It appears that even in the RRMS group there are subclasses - as yet not confidently identified - that make some people respond very well both to steroid infusions and to the DMDs. It "appears" that the basis of this is how much of their disease is in initial inflammation and how much is in direct neuronal or axonal (nerve body and fiber) degeneration. Some people have fewer T2 hyperintense lesions, yet have a lot of disability. They have relapses, but fewer and the DMD's seem to have little effect. I am definitely one of those. My neuro has commented that he feels I have litte inflammation.
If people who are not going to respond are thrown in with the people who will really benefit, of course the outcome will show little difference. If we could tell - as by a biomarker, preferably a blood test, then I am confident that the results and their "intervals" would be quite different. Daisy - you quoted the study above that mentioned whether someone would benefit could be determined by a blood test, yet the test wasn't mentioned. Several such biomarkers have een touted in the past and been discredited, such as BMP and MOG. Does anyone know what the test mentioned above was for?
I wrote another time about the various ways in which people's MS can be categorized. It shows that this is definitely not a homogeneous disease. After decades of research we still have not found a single or real combo of factors that determine who will get MS nor who will respond the one of the DMDs.
The truth is that some people respond VERY well and the use of a number like 30% responders does them a great disservice. Heck, if we have no known guaranteed treatments, would I try a treatment that 3 out of 10 did very well with and nothing else was offered? Given what I am steadily loosing - YES, I WOULD!
Until we have some way of being able to reliably determine who might be helped and who not - then I feel the DMDs should be offered to all with encouragement, hoping that they will be in the minority group who will see great benefit. The discussion should be clear that most people don't, but some do and some do very nicely.
Steroids are mainly immune-suppressants rather than modulators. The majority of the MS field believe they can play a definite role in limiting the acute damage, but I have not heard anyone who believes that merely treating with enormous doses will actually effectively treat MS.
4mg of Medrol is 1/250 of the recommended dose in MS. One of the known side effects for the majority (not everyone) of low dose steroids is euphoria - plus an increase in the feeling of well-being - plus, also an increase in energy. This makes it easy for people to believe that the low, oral dose is having a good effect on the disease. I think some neuros get sucked into this also.
Surth - You asked if the use of IV drips of steroid can be sufficient for relapses. The answer, if you read all of the above is probably not. The DMDs offer more hope of "some people" really benefitting, but the percentage is not large. However, if you are one of the ones that does benefit, then it's 100% that you will be helped. This won't be known until you use it or a marker to tells us that you are in the group that will be helped is found. Unless you are in the about 12% that will stay mild through your whole life, then your risk of deterioration is pretty much 100%. I would opt for 30% chance of improvement over 100% chance of deterioration any day. At least there is hope.
You also asked about the genetics of MS. The information you were given is incorrect. And remember that the chances of MS change dramatically from near the tropics to higher lattitudes (greater distances from the equator). Overall in the US the chance of developing MS is about 1 in 800 higher in the northern states and lower in the South. It depends mainly where you spent the first 15 years of your life.
If a first degree relative of yours has MS the chance of you developing MS drops to about 1 in 50 for a parent, about 1 in 25 -30 for a sibling or fraternal twin, and about 1 in 3 for identical twins. So, there is some role of genetics, but it is affected also by lattitude of youth, the Vitamin D status of your mother during gestation, season of your birth, having had the severe form of Epstein-Barr virus, called Infectious Mononucleosis. The role of CCSVI - whether is is a part of the cause or a side-effect of the disease - is not known.
CAn it be treated by LDN? There are thousands of people who claim that it has helped. There have been three good, scientific studies - all small. Two found no short term improvement on relapses or lesions, and one that showed a modest improvement in relapses. One of the studies showed a worsening of quality of life and the other two reported improvement in quality of life.
Here in the forum we have had many people try it and they seprarated into three groups, some felt better, some felt unchanged and come continued to worsen as they had before gowing onto it.
Diet - There is no evidence that diet either causes or treats MS. However, many people feel better on specific diets and I say go for anything that is not harmful if you feel better, even if it is placebo. YAyyyy for placebo!
Quix - President and Foundation of the support group for people who talk too much
This is the information about the blood test as well as the link to the article.
In MS, a subset of CD4 cells called Th1 cells direct an inflammatory immune response against myelin. Beta interferon dampens this signal, so it's a great help to people with MS -- at least, to those who respond to treatment.
Why doesn't beta interferon always work for MS patients? A clue comes from a little known but equally devastating disease called neuromyelitis optica (NMO). In NMO, the immune system attacks nerve fibers, but it targets a protein different from myelin, says NMO researcher Michael R. Yeaman, PhD, vice chair of medical sciences at Harbor-UCLA Medical Center.
NMO researchers have shown that the CD4 cells behind NMO aren't Th1 cells, but another type called Th17. Might Th17 cells cause some cases of MS?
Yes, Steinman and colleagues found. First the researchers induced an MS like disease in mice using either autoimmune Th17 or autoimmune Th1 cells. Then they showed that beta interferon improved MS-like symptoms in mice with Th1-induced disease, but that the drug worsened MS symptoms in mice with Th17-induced disease.
Humans, too, appear to have different kinds of MS. Steinman and colleagues tested blood samples taken before treatment from 26 MS patients. Six of the 12 patients who did not respond to beta interferon had high levels of Th17 in their blood.
These patients with Th17 immune responses also had high levels of beta interferon in their blood -- before beta interferon treatment. That means one of two things:
In patients with Th17-type MS, beta interferon doesn't help because beta interferon levels already are high.
In patients with Th17-type MS, beta interferon doesn't fight inflammation -- it makes inflammation worse. In this case, just as in mice with Th17-induced disease, beta interferon would exacerbate MS.
People with MS are likely to see a benefit long before new treatments emerge. Blood tests already exist that can tell MS patients whether they have Th1 or Th17 disease. Those with Th17 disease can be spared having to undergo the side effects of beta interferon treatment, while those with Th1 disease can endure side effects knowing that the treatment is highly likely to work.
In a specific variant of NMO, Optico-spinal MS (Asian variant MS - also know as NMO with spinal lesions) there seems to be good statistical correlation to people with specific HLA allele sequences. This seem to indicate that this may be a different entity altogether. If my memory is correct this is also an entity that doesn't respond well to the DMDs.
That indeed is promising, but the numbers are so small I would like to see what percentage of MS patients fall into just those two categories. Only half the non-responders were Th-17 positive. What about the other half? I still looks like something is missing. It seems like an early finding to make such a pronouncement. It would be fabulous if a large number of the participants of the studies you quoted would be tested for the CD4 typing. Then the numbers could be run, at least roughly, to redo the findings. What would be the percentage of people helped by interferons who were Th17 positive versus negative.
I have seen studies before look like they had the key - as I mentioned, the MBP and MOG protein levels in the serum - only to be shown later, in larger studies, that the correlation was not as strong as it had first seemed.
BUT, taking this information at face value, I would bet anything that I would be in the Th17 category. I got no relief from any of the steroid infusions and no difference was see after a year and a half of Avonex - except increase in depression.
Okay, this is a very interesting article published this last spring in the journal, Nature. They found what we said, except that only 6 of 14 people who did not respond to beta-interferon were found to have Th17 CD4 cells. They are developing a more sensitive method for determining Th17 that they think will be able to pick up 80% or so instead of 40+%. They did not mention in the form that I read how many of the non-responders who did NOT have Th17 cells but did have high levels of circulating interferon-beta in their bloodstreams.
I could not find any followup or companion studies to see where this line of research has led. They stated their intention to go back and retrieve plasma from certain studies to see if this finding really does correlate with DMD (Interferon) responders and non-responders. They want to test 10 or 100 times the number of people as in the initial study. I should be a researcher, I guess.
So, this is Not Ready for Prime Time. It's a very interesting, but unproven idea that may in the future give us a better idea for guiding patient med selection. Our best hope is still the recommendation that people start a DMD and start it early.
I am going to add this distinction to the others we have already talked about and we'll watch for developments.
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