The Drug/MRI Fallacy

[Kronk]

I hate to defend Copaxone… BUT

The 2004 Cochrane review was damning, but I disagree with the statement that the study proved it was “…all but useless…”. The review concluded that glatiramer acetate "did not show any beneficial effect on the main outcome measures in MS, i.e. disease progression, and it does not substantially affect the risk of clinical relapses." Substantially is a difficult word to define… I believe like any other medication it works for some but not all. The Cochrane study was done in 2004 with data that was who knows how old. No MS drug claims to prevent progression of disability, but many studies since the Cochrane one have shown it does affect progression to SPMS.

A 15-year followup of the original trial compared patients who continued with glatiramer to patients who dropped out of the trial. Patients with glatiramer had reduced relapse rates, and decreased disability progression and transition to secondary progressive MS, compared to patients who did not continue glatiramer. There were no long-term safety issues.

Also the fact the FDA refused it at first was likely due to the wording of the original submission. Once re-tooled it was approved for FDA for “reducing the frequency of relapses, but not for reducing the progression of disability.” Like all other MS medications. The original submission did not differentiate between these two facts and since data at the time did not clearly show any effect on progression to disability it was rejected. FDA doing a good job, AMAZING

In two recent studies, both reported at the 2007 ECTRIMS meeting, the efficacy of glatiramer acetate was compared to high-dose/high-frequency interferon beta with results from 2 studies. In the REGARD study, Rebif was compared to glatiramer, and in the BEYOND study, Betaseron was compared to glatiramer. In both trials, there was no significant difference between interferon and glatiramer in the primary endpoints (time to relapse) or in any clinical endpoints, although some differences in MRI measures of disease activity have been claimed.

Basically it is not better than any of the other MS medications, but at least it doesn’t suppress your immune system.

Another interesting bit of info is that Copaxone has FDA approval for clinically isolated syndrome, based on the PreCISe trial, which showed that glatiramer delayed the progression from the first clinical event to clinically definite multiple sclerosis with a risk reduction of 45%. 43% of patients in the placebo group converted, compared to 25% in the glatiramer group. Those are substantial numbers, and I think this speaks to its ability to protect the Blood Brain Barrier or act as a decoy for the myelin activated T-Cells.

[HarryZ]

I hate to defend Copaxone… BUT

Of course you would defend Copaxone...it has helped you... I would do the same!

A 15-year followup of the original trial compared patients who continued with glatiramer to patients who dropped out of the trial. Patients with glatiramer had reduced relapse rates, and decreased disability progression and transition to secondary progressive MS, compared to patients who did not continue glatiramer. There were no long-term safety issues.

It would have been a better comparison if they had used random MS patients as opposed to those who had dropped out of the glatiramer trial. They dropped out of the trial for likely a very good reason....Copaxone wasn't doing very much for them, perhaps it was making them worse or they just weren't going to respond to DMD therapy. Using the drop-out group liekly guaranteed better results for Copaxone users.

Also the fact the FDA refused it at first was likely due to the wording of the original submission. Once re-tooled it was approved for FDA for “reducing the frequency of relapses, but not for reducing the progression of disability.” Like all other MS medications. The original submission did not differentiate between these two facts and since data at the time did not clearly show any effect on progression to disability it was rejected. FDA doing a good job, AMAZING

Guess it depends on who was doing the analysis of the original submission. I was told that it was more to do with not reaching the end points at all so who knows.

In two recent studies, both reported at the 2007 ECTRIMS meeting, the efficacy of glatiramer acetate was compared to high-dose/high-frequency interferon beta with results from 2 studies. In the REGARD study, Rebif was compared to glatiramer, and in the BEYOND study, Betaseron was compared to glatiramer. In both trials, there was no significant difference between interferon and glatiramer in the primary endpoints (time to relapse) or in any clinical endpoints, although some differences in MRI measures of disease activity have been claimed.

Ah, the head-to-head trials between the drug companies! Millions of dollars spent trying to prove "my" MS drug is better than "yours". The disappointment among them would have been large, especially the marketing/sales people. But hey, that's all these companies had to do to pay for these battle trials is raise the cost of their drugs to the MS patients which they have done many times. Instead of the price of these medications dropping over time, they have gone exactly the other way.

Basically it is not better than any of the other MS medications, but at least it doesn’t suppress your immune system.

I guess that's good unless you happen to get a great dose of lipoatrophy (spelling?) by using it.

Take care.

Harry

[zjac020]

As for the PRECISE trial...how did they control that patients only did DMDs? How did they control that patients made non lifestyle changes whilst in CIS? I.e. no change to diet, or stress, or exercise, or rest, etc. All of this is what I, and sure many others do after the CIS diagnosis. Does anyone still believe lifestyle changes aren't a major factor in relapses? So...how did they control to ensure those patients continued with life in exactly the same way as before the relapse?

[Kronk]

Of course you would defend Copaxone...it has helped you... I would do the same!

I just hate to work for free, there sales reps make big money

I guess that's good unless you happen to get a great dose of lipoatrophy (spelling?) by using it..

Its a risk for sure, but as I stated in another thread its very rare in men, and I maintain a bodyfat around 10% so I am not too worried.

Ah, the head-to-head trials between the drug companies! Millions of dollars spent trying to prove "my" MS drug is better than "yours".

Very true... I wish they would come to the realization that by treating the immune system component you are treating a fraction of what this disease is, so attaining more than a 30% efficacy is unlikely. The one standout is Tecfidera, but many (including me) think its mechanism of action is more likely attuned to correcting a deficiency in the KREBs cycle. Fumaric Acid is what is produced by Vitamin D when your skin is exposed to sunlight. But if you think of adding it to your regimen you may as well eat a pack of gummy bears, as they have a ton of fumaric acid in them. Only the esthers are bio-available but you can get them without spending $30,000 a year. A lot of psoriasis meds are sold over the counter, I take one called psorex.

As for the PRECISE trial...how did they control that patients only did DMDs? How did they control that patients made non lifestyle changes whilst in CIS? I.e. no change to diet, or stress, or exercise, or rest, etc. All of this is what I, and sure many others do after the CIS diagnosis. Does anyone still believe lifestyle changes aren't a major factor in relapses? So...how did they control to ensure those patients continued with life in exactly the same way as before the relapse?

I guess they expect that any changes in diet vitamins or any other lifestyle change would be reflected on both sides of the fence. But your point is valid, i recently read a study that said placebo arms of MS trials are doing better than ever! This is being credited to lifestyle changes, Vitamin D supplementation etc. So yes, making changes in your diet, exercise, stress levels, make a profound difference on the course of this disease. I am in the best shape of my life, and in the best mood of my life, unless I start thinking of the future and what it may bring. so I choose to focus on the NOW. The future and the past hold nothing for us but regret and anxiety.

[centenarian100]

Cheerleader already posted several references.
http://www.thisisms.com/forum/general-d ... ml#p221165

none of these are high quality randomized controlled studies where liberation performed better than placebo in disability, relapse, or MRI outcomes.

[centenarian100]

Can't count the number of times I read from the established MS world of medicine that a cure was "just around the corner!" This is biggest corner I've ever seen in my life. Every year there has been another promising drug that fixed MS in that poor EAE mouse only to fail miserably when tried on human MS. Guess they were part of the 990 bogus group.

everything works in EAE

So is it any wonder that anecdotal reports of benefit have surfaced so often with MS. While not counting scientifically, anecdotal evidence has fueled many arenas of excitement that have helped some MS patients. Would a patient use a powerful immune system altering scientific drug will all its possible fallout or try something with anecdotal evidence that doesn't harm you if it does nothing for your MS? Difficult decision to say the least.

I personally think it is reasonable to consider unproven treatments if they are inexpensive, safe, and biologically plausible. I think the best example of this is diet because a lot of diets designed for MS (terry wahls, swank, etc) are generally healthy and probably reduce the risk of cardiovascular disease, so you can't lose. Also people generally feel subjectively more energetic if they are keeping a good diet.

So basically, I agree with you. However, I think that people should make reasonable claims based on the degree of evidence. For instance, Terry Wahls should not be marketing her diet as a cure for MS. She should state that it is an unproven treatment that she believes is biologically plausible given some evidence for a role of mitochondrial/metabolic failure in progressive MS, and that she and some others have anecdotally improved after implementing the diet.

[centenarian100]

Kronk-I think the cochrane review is just pointing out that copaxone has poor data for disability compared to other DMTs. I think that this is a fair criticism.