Fred Lublin, MD: Patricia, why don’t you tell us a little bit about glatiramer acetate [GA]?
Patricia K. Coyle, MD: Glatiramer acetate consists of random polymers of 4 amino acids. It is a biophysical analogue of myelin basic protein. It was discovered at the Weizmann Institute of Science where they were looking at peptides that induced an animal model of MS [multiple sclerosis] called EAE [experimental autoimmune encephalomyelitis], and glatiramer acetate paradoxically protected against it, so they began to study it in MS. Glatiramer acetate has 2 major claims to fame. Number 1, it’s the only disease-modifying therapy [DMT] that requires no laboratory monitoring whatsoever. That’s a stamp of approval with regard to great safety and tolerability. As pointed out, it is not immunosuppressive. It’s an immune modulator as are the interferon-betas.
Secondly, it has the widest human pregnancy exposure. Thousands of cases, absolutely no signal, at least hundreds of women with MS treated during pregnancy. You don’t need a washout; you could use it during pregnancy, and you can use it with breastfeeding. Those are 2 dramatic statements that promote it. Very safe, no monitoring, the best documented DMT for pregnancy. The mechanism of action is not known for sure, but it creates regulatory T cells that appear to be helpful. It shifts to a T helper 2 type profile, so there’s a cytokine switch. It has a potent effect on antigen presenting cells, so there is an innate immune component to glatiramer acetate, and you see increase in neurotrophic factors like BDNF [brain-derived neurotrophic factor]. All of those have been postulated to perhaps be mechanisms of action, although, precisely, we’ve been using it for years, we really don’t know.
Fred Lublin, MD: Good. Wallace, thoughts on GA?
Wallace Brownlee, MBChB, PhD, FRACP: Like the interferons, there is still a role for this injectable therapy, but the role is diminishing. It can be a particularly attractive treatment option for women who are planning pregnancy, and again, for patients with comorbidities.
Fred Lublin, MD: Sven?
Sven Meuth, MD, PhD: There’s not much left to add. I can only support Wallace and Patricia. This is the same reason why we are still using glatiramer acetate in Germany, especially for patients starting family planning and based on the safety profile of this drug.
Fred Lublin, MD: This one has been interesting in the terms of the population that comes in. There is a population of patients who come in to see us, and when we start to talk about disease-modifying therapies, they’ll say, “How long has that drug been around?” As soon as they ask that question, I know where the conversation is going to go because then they’re going to say, “Well, I worry about what I put in my body. What’s the safest thing you have?” Now, we know there are some people who come in and say, “What’s the best thing you have?” But there’s a significant percentage who come in and say, “What’s the safest thing you have,” because they worry about it. They worry about adverse effects and things of that sort. That’s the group that I start and still start on glatiramer acetate for just that reason.
The other is, as was brought up, people who are thinking about planning a family sometime soon. It’s a very good agent to deal with in that regard. Of course, like interferon, because GA came out in 1997, we also have a large cohort of individuals who were taking their injection, most of them switched to 3 times weekly from daily, who also said, “I don’t like these injections, but I don’t want to switch because I don’t want to mess with success,” and that holds for GA as well. The other thing, as you brought up, Sven, I can think of 1 patient who was being treated with chemotherapeutic agents and also needed to have their MS treated, and it was a good addition in that situation.