Patricia K. Coyle, MD: When we’re talking about switching disease-modifying therapies [DMTs], there are many reasons why somebody might switch. One reason would be that the person is not tolerating the medication. It may be working well but causing them pain and suffering and poorer quality of life. If you’ve done your best to manage adverse effects, that’s a legitimate reason to switch. Or somebody might have an abnormal laboratory finding on their white cell count or their liver, which may mean that this is becoming problematic, and that’s another valid reason to switch.
Another big reason to switch is unacceptable breakthrough activity, in which somebody has more active MS, and the disease-modifying therapy that was chosen doesn’t seem to have the efficacy to really control the MS damage process sufficiently. If you had a patient on an oral agent and they were having breakthrough activity or disease activity, you want to switch them. You don’t want to sit there and have that going on, but you rather want to switch them to what you would perceive as a higher-efficacy agent, and that’s probably a switch to one of the monoclonal antibodies.
There, you’re going to be thinking, “Well, that’s great. I want to put them on a high-efficacy agent, but what is the risk of the high-efficacy agent? What monitoring do I need to do? How can I discuss with them what their options are?” And remember, we have 3 high-efficacy monoclonal antibodies. I think you would sit down and go over that, but the bottom line for breakthrough disease activity would be to make a switch to another DMT that you perceive as having a different mechanism of action had higher efficacy.
Clyde E. Markowitz, MD: Sometimes, we have to switch treatments for patients if they can’t tolerate a medication or if there’s a safety concern that comes up. Maybe the efficacy of the drug is not adequate. We look at this, and we factor in, “OK, so they’re on this treatment, whichever one it is at this point. We need to know whether or not the drug has had its full benefit in the time frame that we hope is appropriate.” Let’s say somebody starts a new medication and they have an attack the next month. Well, it may be too soon to make a determination if that medication is inadequate. We might say 3 months is probably not a bad idea. Some people like 6 months. It depends on the drug. It depends on when that drug becomes fully active and what you would expect to see in terms of suppressive disease activity.
But when we look at patients, we look at their clinical features. We look to see whether or not they are having attacks. We look at their MRI [magnetic resonance imaging] scans to see if they have new lesions or active lesions. And then we look at a variety of other metrics, such as their fatigue or their cognition. We worry about safety concerns, monitoring their blood and seeing if there are any other body issues going on, whether high blood pressure or cardiac issues or pulmonary issues.
We have to monitor all of that. If we find anything along that route that gives us concern that either they’re inadequately managed or there’s a safety profile we’re worried about—their liver enzymes went up or their white blood cell count got too low—we may have to make a switch. Sometimes that switch is fairly straightforward. Sometimes we have to worry, depending upon what drug they were on. Where they’re going to go next may be a problem because there could be sequencing issues there, where you may have to wash your drug out for some period of time before you start a new drug. You may not want to wash that drug out because you need to have a tail on it or the disease activity is going to come back, so you need to start a treatment right away.
There are a variety of pieces to that. One of the other pieces that we have very little control over are the insurance companies. Unfortunately, they have an opinion about sequencing sometimes, or they say, “Well, this one is approved in our plan, but this one is not, so I can’t let you use that. You’ve got to try this first,” which drives us crazy. But the truth of the matter is, we know how to use these drugs from an efficacy and tolerability standpoint. We know the patients, we know what their concerns are, and we know what the issues related to x, y, and z are, so we should be making these decisions.