Dr. Boster: With the newest diagnostic criteria1, we're diagnosing MS very, very early; and in the last 10 years we've learned that if you put people on therapy sooner, they do better long term. CIS is just the beginnings of what's going to go on to be MS. So, putting these people on therapy, in my opinion, is very important.
Now, you're weighing some risk and benefit here. My standard practice, up until the oral agents came about, was to use glatiramer acetate first-line for CIS. The PreCISe trial supports its use, and glatiramer acetate has a very attractive side-effect profile.2 And, when you have a patient with CIS, they don't necessarily fully understand the disease process; they most often are asymptomatic after they recover. And so asking them to buy into a therapy that they'll take for the rest of their lives, early on in this condition, is challenging. And if there are a lot of side effects, there's a high likelihood that they're going to be nonadherent. And so, I've had success in my own personal clinic managing CIS, particularly CIS at high risk, by starting glatiramer [acetate].
One could consider interferons. My opinion is that the side-effect profile with the interferons—with flu-like symptoms and possible worsening of depression and spasticity, and headaches—may make them slightly less attractive, although they’re still a viable option.
The oral agents are game-changers in some capacity. Patients generally feel more comfortable taking a pill than a shot. And when you're dealing with a CIS population, these are people that aren't completely invested in their disease yet; some of them don't really believe yet that they're going to go on to have MS. When I look at the oral agents available, dimethyl fumarate is very attractive. It has good data in a population of very young, new MS patients, not CIS but a similar population. And at first blush, it appears to be very safe and well tolerated. If you look at the DEFINE and the CONFIRM trials3,4, the pivotal trials that led to the FDA approval of dimethyl fumarate, the majority of those patients were treatment-naïve. And the majority of the patients had relatively early disease.
I would be less comfortable starting teriflunomide in a CIS patient. We don't know how that patient is going to go on to develop and how aggressive their disease will be. In my opinion, given that teriflunomide is an immunosuppressant, this may close a door for natalizumab downstream. And I think the ordering of drugs becomes very important.
One could consider placing a CIS patient on fingolimod.5 It's a highly effective medicine. The one challenge in the CIS population is the number of safety checks that have to be done before starting the drug. If the patient is willing to go through the rigor of the evaluation, then I think that fingolimod is an option.
In summary, when I'm looking at a CIS patient, particularly a CIS patient at risk, the two drugs that I'm more likely to reach for would be glatiramer acetate and dimethyl fumarate as a viable option.