Optimizing Treatment Selection in Multiple Sclerosis

Robert J. Fox, MD: When I talk to patients with MS [multiple sclerosis] about goals of therapy, there are 3 main goals that I relate. One is that we're trying to decrease and ultimately prevent further episodes, further relapses of MS. I also want to prevent new lesions on MRI [magnetic resonance imaging], because those new lesions on MRI represent additional manifestations of the disease that the patient doesn't even recognize. Ultimately, I want those 2 things to then stop the progression of disability, stop them from accumulated neurologic deficits from the injury of the relapses and the lesions on MRI. So, it's those 3 goals: preventing relapses, preventing new lesions, and preventing gradual or accumulated disability.

Our first therapies for MS that were developed in the late 1990s were injectable therapies. These were interferon and glatiramer acetate. They were originally identified in animal models, and were found to decrease relapses and new lesions on MRI. They were modestly effective at best, and when direct comparisons between the different injectable therapies were done, they were actually found to be much more similar than they were different. In the early to mid-2000s, we then developed new lines of therapy.

Two new lines of therapy emerged. One was oral therapies. These were clearly more effective than the injectable therapies, and had the obvious advantage of being oral. Patients didn't have to inject themselves with once-a-day or once-a-week injections. The patient acceptance of these oral therapies was, as you can imagine, much better; and so was the efficacy. It became clear that these oral therapies were more effective.

In parallel, and since then, we have also developed infusion therapies. The infusion therapies have mostly been monoclonal antibodies that address very specific components of the immune system, and have been found, in general, to be very effective—probably more effective than our oral therapies. They also have good acceptance by patients because they are administered less frequently—once a month, to once every 6 months, or even once a year. Patients find that very infrequent administration schedule to be very attractive.

Fred D. Lublin, MD: The biggest challenge in optimally treating patients with MS is trying to determine the best therapy for any given individual. We don't have an algorithm—start with A, go to B, then go to C—and we can't really afford to have people have a lot of activity because it does permanent damage. We also have to take into consideration all life events that affect when a person goes on therapy: Things like risk aversion, and family planning for women who are planning pregnancies rather than going on our therapies.

We don't have a biomarker of response, which would be nice. Because MS is such a variable disease, you can't easily measure therapeutic response. Just by natural history, patients can go for a long time between attacks. So, that's probably the biggest challenge we have in that.

We have—I've lost track of how many—18, maybe more, agents approved for use in multiple sclerosis. They are all effective in some individuals. As I have said, we don't know how to pick a given agent based on someone's therapeutic response. There's no biomarker of success. So it's become a longer and longer conversation to try and pick out the best therapy for a given individual.

This is a good problem. It's a good problem because we have choices. If someone is not suitable for 1 agent because of a comorbidity, or because they're JC [John Cunningham virus]-positive and may not be suitable for another agent, we have lots of choices.

We also have some choices that are better for someone who's planning for a family soon. We don't yet have really good therapies for progressive disease. We have a start in both primary-progressive and secondary-progressive, but that too is a major challenge for us now in trying to find better therapies to deal with progressive disease.