What’s the Progression of Multiple Sclerosis With Treatment

The second point I want to make about treatment is that drugs are only partially effective, and there is not a single study that compares them that is widely accepted as medical fact. In fact, for every study that suggests that one interferon may be slightly better than another one in clinical outcomes, there are four or five which suggest that there is not a lot of difference. I think in order for us to adequately compare the effects of treatment versus non-treatment, we must rely on the Phase Three studies of these various drugs.

And what is a Phase Three study? That is a study that looks at the particular drug versus those individuals who don’t get the drug – what we call the placebo group.

Some of you on the Internet have a Venn diagram picture of what I think are three important areas to talk about. One is clinically, how do you do? How many attacks do you have? What about your disability? Then another part of this thought process of how these drugs work relies on looking at your MRI findings. Finally, how do these drugs affect cognition, or how you think?

When we look across the board here, we find that these drugs are effective, but to a variable degree. When we look at clinical outcomes, we find that all of the drugs – ABC drugs, including Rebif – affect the relapses by about 30%. Avonex and Rebif also affect disability progression. Copaxone and Betaseron had trends towards that but didn’t reach statistical significance. But in fairness, the major outcomes of those studies were mainly looking at relapses.

When we look at MRI outcomes, we find that all these drugs again positively affect the MRI – they reduced the activity seen on your MRI scan. Some of them also have demonstrated effect on reducing brain atrophy. Avonex, for instance, has been shown to demonstrate a reduction of brain atrophy, particularly after the first year of therapy, into the second year. Copaxone also has demonstrated atrophy. Here at the University of Pennsylvania, a very small study suggested that it also affected brain atrophy, although another study, which was very short duration, didn’t demonstrate any benefit to atrophy. Regarding Rebif, there is no evidence that it significantly affects atrophy by the methods we used to test it.

Finally, thinking function. I think this is an area that really requires more attention. That is, how people interact socially and occupationally on a daily basis, and how things are working out for them in their interactions with the thought processes. We found that Avonex versus placebo – those patients who got placebo didn’t fair as well cognitively as those that were on Avonex. In the Copaxone trial there was no difference in cognitive capabilities between those patients who got the Copaxone versus those who were on placebo. We don’t have information about Rebif in this regard. Regarding Betaseron and cognitive function, only one out of nine parameters tested in thinking were found to be positively affected by the drug.

I think the summation of these trials across the board really emphasize the role of treatment versus I think the summation of these trials across the board really emphasize the role of treatment versus those patients who didn’t get treated. We see that in all these very important parameters – their clinical outcomes, their MRI outcomes and their cognitive outcomes – that the drugs may positively affect their long term. When we couple this information, I think it just emphasizes that early treatment is indicated.

I think when we look even years down the line here, now that we’re getting five, six, seven years from these trials, and we’ve looked back at the patients who got placebo, even if they got on drugs two years out from when that study started, they still are not caught up with those patients who were immediately placed on the drug in the clinical trial. They have more activity, they have more disability, their MRIs aren’t as good as those patients’ who were initially on drugs. So I think that this really hammers home the point for early therapy.

This is also verified by the fact that when we have placed patients in the very earliest stages of MS, the patients who have had one typical attack with a positive MRI suggesting that they have early multiple sclerosis tended to fair the best in terms of reduction of the next relapse. What I’m referring to here is a study that’s called the CHAMPS study, which looked at patients who had a single attack. Say they had optic neuritis, or a loss of their vision in one eye and they had an MRI that showed lesions. Those who got Avonex versus those who got nothing had a 44% reduction in having the next clinical attack.

This also is verified by a European study that looked at Rebif in patients with a single attack versus those who got nothing, and demonstrated a 24% reduction in having the next clinical attack.

We see that these two studies early on, even when we use just once-a-week dose of Rebif, had a positive effect in reducing the next event. I think there are a few other very important reasons why one should consider early treatment, and that is the fact that we’ve learned from these trials – the CHAMPS study in particular – that brain atrophy begins at the earliest stages of disease, and that is to say that those patients who were in the CHAMPS study, who were monosymptomatic, those patients were demonstrating evidence of atrophy even at that stage.