This Is MS Multiple Sclerosis Community: Knowledge & Support

Sorry, time to leave the board.

-finn

Every time a report comes out it appears to contradict another, however, I have just switched to copaxone despite having read the Cochrane report. I see what you are saying about critising trials, that is a very fair comment and may have an impact on the design of future trials. In the case of copaxone I am not convinced by the review because...

1. I believe it ignores MRI evidence and open label trials- focussing only on double blinded placebo trials focussing on EDSS outcomes. However, copaxone as far as I am aware, (with the exception of the PPMS trial) has not been in a trial where the overall purpose was to examine the impact on disability.

2. Copaxone does demonstrate impact on MRI in regard to reduced black holes. Maybe it's neuroprotective attributes are drug company hype, who knows.

3. I don't know of any open label clinical trial that does not show copaxone having an effect on relapse rate.

4. Copaxone works slower than the interferons but this doesn't mean it has no effect as the latest study (link below) that came after the Cochrane review show.


http://www.docguide.com/news/content.ns ... AD0055CA3E

http://www.docguide.com/news/content.ns ... s&count=10

At the end of the day, for me, if there is even the remotest chance it will slow atrophy I am willing to give it ago. Obviously not having to pay for the meds helps alot in making this decision so simple!

The side affects are minimal, it doesn't interfere with my life (5 minutes max everyday) so until something better comes along I will stick with it.

Felly

Felly,



Somewhere along the line of MS clinical trials, the focus has shifted to how well the MRI pictures end up looking. Once upon a time it was important to see if the drug reduced or slowed down the disability of the MS patient and how the patient actually felt. Since there is little correlation between brain lesions and MS symptoms and the patients in most cases don't feel well at all while on these potent drugs, the drug companies have to focus on something positive. And that appears to be the pictures!!

I guess from a marketing point of view, that helps bring in the revenue....but from a MS patient point of view, I really wonder.

Harry

The point I am trying to make (and badly, sorry) is that the copaxone does appear to reduce black hole lesions - that is significant to me -and the MRI can/dose reflect this reduction in brain atrophy. So in ignoring this as a measurement of copaxones efficacy makes little sense.

The cochrane review is reliant on the EDSS measurement of disability but the EDSS is not perfect measure of disability at all. At least not for me and a number of people that I know.

I believe it places too much emphasis on mobility and ignores clinical change. On the EDSS scorecard I remain at 0.0- even when I am having a relapse I remain at 0.0-yet I have a couple of black hole lesions and have definitely lost some cognitive functioning along the way but if I'm measured by EDSS then I should be climbing mountains and competing in this year's olympics. In the world accoring to the EDSS I cannot possibly be in anyway affected by my MS. Bull. So I don't agree that the review should have ignored these trials and I think it is time a better measurement outcome is found.

Copaxone has been shown to reduce black holes and this can only be seen via an MRI study. It's not just about a prettier picture it's about the possiblity of me having less irreversible brain damage.

Felly

I can safely say that I and a lot of people on this site learn more from Fell, HarryZ, and Finn than any neuro.

Thanks and keep it going!

I cannot agree more, Wilson. Thank you to these outstanding individuals (and others such as Shayk) for sharing their time and knowledge with the community.

For the quieter members of the group-- please don't be shy to speak up and do the same kind of research to share with the rest of us. This kind of individual initiative benefiting the group is what our site is all about.

I think this collective on-line community DEFINITELY knows more about MS than the neurologists I've seen.

As far as the Cochrane reviews, I have read them with great interest. The focus on EDSS seems limiting to me- and the measurement of MS in general seems a very imprecise science. It would certainly be possible to measure disability more accurately- by using a combination of MRI, neuropsychological testing, self-report, EDSS, and other measures.

The fact that we haven't seen such measurement makes me cautious about ALL MS drugs.

I know for instance, in the case of SSRIs, they have administered Quality-of-Life scales in over 100 trials. They have never published the results. The reason (it is now revealed) is because while SSRIs do improve certain symptoms, they do not have a statistically significant effect on Quality-of-Life, as measured by these scales.

But if these data had showed a positive effect, you can bet your a$$ they would have trumpeted these drugs as improving quality of life.

So we have to keep in mind that at present, the pharmaceutical companies are able to get by with imprecise measurement and are allowed to withhold any data they find inconvenient.

It's quite possible, for instance, that they do collect data on self-report of disability, but it hasn't been good enough to report.

Cochrane is good- but not perfect. If we wanted a real frank assessment of what these drugs actually do, we would need full disclosure of the data.

But I really think all the ABCR drugs can be summarized as, "Mildly to moderately effective in the aggregate, but the best we have at the moment." That would be honest.

Finn, I for one, an Avonex user , really appreciate your bringing information from the Cochrane Reviews to our attention. I actually use the Cochrane Reviews in my work. It never even dawned on me to use them to assess the CRAB drugs. I’ll blame it on the MS.

Your point that the Cochrane Reviews criticize the way CRAB drugs have been studied in clinical trials is the point as far as I’m concerned.

I'd echo everyone's comments and maybe emphasize Daunted's. The drug company clinical trial designs and outcome measures are one thing, what they don't report is another.

An article in today’s New York Times “Medicine’s Data Gap”, has the following headline: Results of Drug Trials Can Mystify Doctors Through Omission. It pertains to FDA requirements for drug labeling.



We need to be concerned about study design and data and we need to know about trials with the CRAB drugs (and, of course all others) that failed. Seems to me we all learn from mistakes at one time or another, or at least we should.

And, BTW, it seems really difficult to find CRAB outcome data (or general MS research) reported by gender. Now you know that really irritates me.

Take care all...you're a great group and I've learned a lot from everyone.

Sharon

Felly,

I hear what you are saying.

At the same time one starts to wonder about the measurements that neuros use when it comes to really determining how a MS patient is doing. Saying your EDSS score is 0 basically states that you are 100% mobile and have no MS symptoms.

I firmly believe that many if not most of the CRAB drug clinical trials haven't been up front with all the info that they have published. A friend of mine, who really knows how to read the fully published trials, has pointed out to me some real shortcomings of these trials. One early Betaseron trial showed that some patients actually were given steroids during the trial which of course masked any symptoms that may have shown. Other patients who had experienced a relapse were removed from the trial and their data was not used!

I can remember attending a research update a few years ago and listening to a neuro give all the wonderful stats about a Betaseron trial that had been completed. I asked a simple question..."did any of the patients in the trial feel any better or have any of their symptoms helped at all while taking the Betaseron" ..."no" was the reply and you could hear a hush come over the people in attendance!

I guess these trials are done to ensure that the drugs can be presented in the best possible light in order to keep the sales as high as possible. So far, I have yet to see any conclusive evidence that the CRABs do very much to relieve the daily suffering of the MS patient and prevent the disease from progressing along as it wants to.

My wife, who has SPMS, takes Prokarin and LDN. She has not had any progression of her disease for over 4 years and her once very severe multitude of symptoms are mostly controlled. This allows her to live some quality of life. I personally believe that this kind of therapy is much better than what the CRABs can do but everyone, of course, has their own opinion.

Take care.

Harry

Sorry, time to leave the board.

-finn

As someone who is going to an academic center shortly and will be likely offered treatment, this is a question near-and-dear to my heart.

I am very happy for anyone that is taking any of the ABCR drugs and finds that they work well for them!

But, that dropout rate concerns me greatly. The most likely conclusion to draw is that the disease is progressing anyway, so the patient discontinues the treatment. And as Cochrane said, if all dropouts were categorized as treatment failures, the statistical significance of Interferons was completely lost.

And Copaxone couldn't be recommended to begin with- by Cochrane, anyway. A recent 10-year study showed that those who remained on Copaxone, progressed much less than those who discontinued it. But this could still be explained: If a person is doing well, they continue the drug (which they believe is helping); if they are not doing so hot, they drop out. And of course some will drop out purely because of side effects on top of that.

This "intent to treat" data analysis strategy is heavily slanted in favor of the active drug, as are the obvious side effects...there is a lot of data collected but not published...so it's a bit scary for me when I see how enthusiastic neurologists are about these drugs.

One thing that may come of the recent SSRI fuss (supression of data on suicide as well as efficacy), is that we may see more full disclosure in the future. That way we could conveniently make informed decisions instead of undertaking a detective-like quest just to find the facts about these drugs.

Why the high drop rate? Hmm, it’s not just the ABCR trials but similar rates exist in trials of many other drugs. It is always hard to find out the real drop out rate as many failed trials don’t publish results.

I was on a Phase 11 drug trial last year for CTLA4Ig, which was halted in the 11 month allegedly because many patients on the lower dosage and the placebo got worse, however, my digging around revealed less savory reasons. If you want to talk about drug company mendacity then this one was a great example.

Anyway, that’s not the point of this post. The trial was a real pain; it involved monthly IV and MRI, plus a whole cohort of very boring cognitive and motor tests. It meant a minimum of 1 day a month at the hospital, sometimes 2 days. Because it was a placebo controlled trial 'theoretically' you didn’t know if you were on treatment or not. The whole time you had to wonder if you actually had the luxury of spending 12 months on a placebo.

That was the main reason for the drop out rate, followed by the fact many patients on the placebo got worse as did those on the lower dose. The ones on the higher dose did extremely well by all accounts.

Having been on rebif and not even suffering the worst of it and hearing the many stories of the hard time people have had on the drug I can also understand why individuals may drop out of a trial. Taking copaxone means injecting everyday – this is a real commitment. I am not scared of needles, but again I can understand if you are having side affects and you also have a fear of needles you may not want to continue. Add in the fact that you may have to spend years on any drug and even then you will never know if it was the drug or you had a naturally slow progression and it’s not exactly an inducement to stay on the drugs eh?

As to the copaxone pivotal US trial, 65% of patients showed on EDSS (yes, I know I don’t like the EDSS but...) they were improved or no worse after eight years of treatment. In patients who received placebo for the first 30 months, only 50% had scores that were unchanged or improved from entry. It's small but I beleive it worth the effort to stay on the drug, if it is not seriously compromising my quality of life.

So why take ABCRs if MS isn’t an autoimmune condition? Well first of all any condition that they don’t know the cause of but affects the immune system is an autoimmune condition until proven otherwise.

This is the question I asked my doctor before going on to treatment, after the first published reports came out about the Austrialian findings- as follows (we email each other, I think I’m his most annoying inpatient patient). I asked by email..

‘if MS is primarily a disease causing nerve cells to die and the role of the immune system in causing inflammation is secondary then none of the DMDs can prevent disease progression regardless of, to a certain degree, their ability to decrease relapses. So lots of side effects, lots of effort and not a great result in the long term’

The answer...
‘At present this is a hypothesis that needs to be tested. It may be that if we suppress inflammation early on in the disease course we stop the neurodegenerative cascade that may be triggered by inflammation. There is no doubt that inflammation is not all good and is associated with axonal damage and neuronal loss in itself. The million dollar question is that inflammation primary or secondary, i.e. occurring in response to say an etiological agent like a virus. ‘

So there you go, that’s why I am on copaxone, until something better comes along.

Felly

Sorry, time to leave the board.

-finn