Combo Fights MS
Fred Lublin, M.D., Neuroimmunologist,
MCP Hahnemann University, Philadelphia, Pa.

Let's begin with the drugs individually. How does Avonex help multiple sclerosis patients?
Dr. Lublin: Avonex is an injectable drug in the class of agents known as interferons, which have been used in multiple sclerosis for six years now. Avonex decreases the severity of multiple sclerosis, cuts down on the number of attacks people have, and slows the progression of disability.
How does Copaxone help?
Dr. Lublin: Copaxone is an entirely different type of drug. It is what's called an amino acid polymer, which is just a mixture of amino acids. Its effects are similar, although probably acting by a different mechanism. Again, it cuts down on the number of attacks people have and slows the progression of MS.
The new treatment combines Avonex and Copaxone. Could patients just double dose on one of the other drugs?
Dr. Lublin: Unfortunately we don't know a lot about dosing of either of these agents because the tests that were done used a very limited number of doses -- only one dose of Avonex or one dose of Copaxone. Furthermore, because these are immunomodulating agents, more is not necessarily better. It's very hard to do these studies using multiple dosages because it takes many patients, and it costs a lot of money. To double the dose now, we just don't know whether that will be effective or not. We would hope that by combining the two, we could get additive affects that will be better than either one alone.
The main goal of this study is the safety issue. Can tell me more about that?
Dr. Lublin: The first thing that needs to be determined about a new treatment is its safety. Although we expect combining Avonex and Copaxone will be beneficial for multiple sclerosis, we have to be certain. There is conflicting evidence in laboratory studies as to whether it will help or interfere. We need to make sure one agent won't interfere with the beneficial effect of the other. That's why we do the safety trial first.
What outcomes of the animal studies raised red flags?
Dr. Lublin: There was one animal study that suggested combining Avonex and Copaxone cuts down the beneficial effect of one alone. On the other hand, there are laboratory studies that show when the two are combined in test tubes, there's an additive effect, and it's beneficial.
In terms of helping the patient, what benefit do you think you're going to see with putting the two together?
Dr. Lublin: Both drugs are partial therapies when taken individually. They cut down on the number of attacks by about 30 percent. There's a percentage of improvement on the MRI scans they have, and we want to improve on that. We don't have any blockbuster new agents that are going to market in the next three to five years. So the next logical progression would be to improve on the therapies we have by combining them.
How many and what types of MS patients are you studying?
Dr. Lublin: We are studying 32 patients at five sites across the country. They are mostly in the early and middle stages of MS, because those stages are the easiest to measure changes in.
I understand the patients are already on one drug and then another is added. Can you explain exactly how the study works?
Dr. Lublin: The patients will come into the study having already been on Avonex. Then they will continue for three months on just Avonex alone and have monthly MRI scans. After those three months, we add the Copaxone, and they'll go for another six months on both agents with monthly MRI scans. Our read out on the safety will be whether there's any worsening of the MRI scans which should provide us a very early and very sensitive test for any adverse interaction.
What kind of changes are you looking for with the MRI scans?
Dr. Lublin: People get an injection of a dye called gadolinium, which shows where there are new changes going on. In multiple sclerosis patients where there's ongoing activity, you see the gadolinium enhancement. Interferon lowers that level of gadolinium enhancement quite effectively. If Copaxone is going to interfere with interferon, we expect the level of gadolinium enhancement will go back up. That's how we're going to read it.
Is there anything else you want to add?
Dr. Lublin: This is a very exciting era for multiple sclerosis clinical research for patients because we never had treatments until 1993. We now have three treatments and we're looking to improve on that.
If this study is successful in showing Avonex and Copaxone work well together without drawbacks, will a bigger study take place?
Dr. Lublin: A much larger multicenter trial to make sure the agents are truly effective will take place. Its goal will be to prove the result of combining the two is better than either one alone.