Efficacy of Disease-Modifying Therapies Review Study

[10yearsandstillkicken]

I have been watching the NMSS site for an offical response to the study. I sent an email again asking when that would be available. The paper is still not available but it was email to me. So this is it in its entirety and provided by : National Multiple Sclerosis Society, Professional Resource Center
Paper Questions Efficacy of Some MS Drugs
May 9, 2008

A recently published paper* reviews results from pivotal, phase 3 clinical trials that led to the approval of the disease-modifying therapies now available for relapsing forms of multiple sclerosis.

The paper makes direct comparisons between the results of the various trials, recalculating available data, and suggests varying degrees of effectiveness between the drugs, depending on the endpoints applied. One of their findings was that in some of the comparative measures, some of the drugs were not significantly better than inactive placebo.

There is abundant proof, published in peer-reviewed journals, that the approved disease-modifying therapies for MS are significantly better than the inactive placebos against which they were tested. Building evidence also suggests that they not only impact relapses but also may slow the progression of disease.

Well-designed, placebo-controlled studies that are done for extended periods of time have represented the gold standard for evaluation of new drugs. Most statisticians believe that it is very difficult to combine and compare results from different studies, as was done for this article. Problems with this type of analysis include the fact that each study used different patient populations (with differences in their recent relapse experience, age, time from disease onset, and many other variables), different outcome measures, different timeframes of study, and even different definitions of relapses and disease progression.

At the recent American Academy of Neurology meeting in Chicago this spring, a statistician (Dr. Gary Cutter, University of Alabama) looked at this very issue and concluded that one cannot make valid comparisons between treatment effects among studies with different baseline risks or populations.

Although direct head-to-head studies could represent a better way of comparing treatments, currently no well-controlled, double-blind, head-to-head phase III studies comparing the current first line drugs approved by the FDA have been performed.
The paper was supported from funds from EMD Serono, and several of the authors work at EMD Serono or Pfizer Inc.; these companies are co-marketers of one of the drugs involved in the current comparison.


*MS Freedman, B Hughes, DD Mikol, R Bennett, B Cuffel, V Divan, N LaVallee, A AL-Sabbagh “Efficacy of Disease-Modifying Therapies in Relapsing Remitting Multiple Sclerosis: A Systematic Comparison” European Neurology (2008;60:1-11).

[mrhodes40]

Building evidence also suggests that they not only impact relapses but also may slow the progression of disease.

Gnash! Arrghgghhhh! If I see that once more I am going to become some kind of activist!

What they are really saying is there is, to date, no real evidence that these drugs slow.....even SLOW....the disease. What they do see is less lesions on MRI.

Considering we now have drugs that virtually eliminate lesions, doesn't it seem obvious that these are not the same thing as the degenerative process that causes progression? Isn't it also obvious that MS is best described by progression not lesions?

[dreddk]

Of course drug companies love pointing to lesions as its so easy to measure even if the correlation with disability progression is quite loose.

It is quite mindblowing the money being spent on drugs like avonex and copaxone that have unpleasant side effects yet quite likely are no better than placebos in terms of disability progression.

I think even more frustating will be how few people will read a study like this to understand the ms drugs efficacy.

[10yearsandstillkicken]

I had my regular appt with my neuro yesterday. And this very discussion came up. He related that some research he has seen recently shows damage to the white matter in the brain not just the lesions/nerves. That damage did not show on the mri of the patient(s) the sample was taken from. That might explain the progression vs lack of lesion activity. Given that I have still been progressing on rebif, we are going to try tysabri. It is choice being damned both ways. Which poison to pick?

[HarryZ]

I had my regular appt with my neuro yesterday. And this very discussion came up. He related that some research he has seen recently shows damage to the white matter in the brain not just the lesions/nerves. That damage did not show on the mri of the patient(s) the sample was taken from. That might explain the progression vs lack of lesion activity. Given that I have still been progressing on rebif, we are going to try tysabri. It is choice being damned both ways. Which poison to pick?

It would be interesting to learn just what kind of damage to the white matter is taking place. If it isn't "lesion forming damage" that can be detected my MRI, then perhaps there is another unknown mechanism at work that is causing the disease progression. That being the case, the claim to fame by the MS drug companies that their drugs reduce lesions doesn't mean very much!

Again, more questions without answers for this lousy disease!

Harry

[10yearsandstillkicken]

I asked him that same question. He mentioned that they dyed the tissue to see the damage. My question was if this damage is the cause of the brain shrinkage I, and many others, have had. He thought it was possible. It is entirely possible and most likely it would seem, that an important aspect of the disease is unknown and possibly untreated by the current crop of drugs. Reducing lesions is probably needed. It would seem logical that protecting nerves from damage is a good thing. But treating only one of two(?) aspects of the disease is like insulating the walls of a house with no roof. It is till going to get awful cold...