Dr. Boster: There are many factors that we have to consider in each individual patient. The first question is, "What drug were they on and what are the risk factors, the side-effect profiles of that drug? And in particular, when they stop the drug, are there any issues—in other words, do you need a washout period? The second issue is what are they starting and are there any unique issues related to starting a medication? Are there any safety checks or tolerability issues that need to be considered? The third issue is the patient themselves and their comorbid medical conditions. So those are the three factors that we have to consider with each and every patient.
Let me talk about a couple of examples. When a patient is taking glatiramer acetate and they're transitioning to an oral therapy—whether the oral therapy be dimethyl fumarate or fingolimod or teriflunomide—that's probably one of the easier switches from the injectable side. There are some practices that prefer to stop the glatiramer acetate a month before starting the next drug. In my own practice, we don't do that. I can't find an immunologic reason or a mechanistic reason why that's necessary. And so stopping glatiramer acetate is nothing more than stopping it and starting the next medicine.
With the interferons, it's almost as straightforward. Again, the party line is to stop the medicine for a month or so before starting the new medicine. I like to, instead, pay attention to risks and what the switch would entail.
We know that interferons can sometimes tickle the liver enzymes and lower bone marrow function, although they generally don't do that very much, and when they do, it's typically not a very robust effect. So, in my practice, I'm not as worried to be frank, about how long I stop the interferon. Instead, I turn to what I am starting. If you're going to start dimethyl fumarate, dimethyl fumarate tends to drop the white [blood cell] count by about 20% or 30%.1 And so you don't want a suppressed immune response. I don't have much of an issue with that with the interferons and glatiramer acetate, but you do want a fresh CBC. The FDA does not suggest that you have liver enzymes [testing] for dimethyl fumarate; [in] our own personal practice, we like to check them.
If you're switching to teriflunomide, then you're most certainly going to be looking at their liver enzymes anyway, and you're going to screen for tuberculosis and obviously for pregnancy, although in my own personal practice, it doesn't change how I stop the injectables.
Starting fingolimod is a bit of a different endeavor, with the safety checks required for starting this agent . When one starts fingolimod, as we're aware, we have to do an EKG and make sure that they don't have certain heart medicines or certain cardiovascular conditions, which may put them at increased risk for a cardiac problem. I still request that my patients have a thorough skin exam, although the risk for skin cancer is very, very low. I require that my patients have an ophthalmologic examination to make sure that they don't have concerns for macular edema. We also have to make sure that they have fresh LFTs and a CBC to start from. Lastly, we need to make sure that they demonstrate immunity to varicella zoster. Now given that it takes about a month or so to go through the rigor of doing all that prescreening, on average, not uncommonly we'll have a patient stop the medicine at the time they sign up for their fingolimod and then they go through their testing for about a month and start the drug. We do have patients that will continue to take their injectable up until the time they switch to fingolimod because they're not comfortable being off therapy for any given period of time.
When one switches from natalizumab infusions to a pill—if you stop the drug, based on the clinical data, it's going to be relatively biologically active and still kind of functioning for about three months. And so we want to wash people off of their natalizumab, but in a safe fashion. Typically, we stop the medication—this is our own chili recipe, not dogma—and we give them 1 g of steroids monthly for three consecutive months. The rationale is that we keep their disease at bay and we allow them to wash off the natalizumab in a safe fashion. At month three, we'll start them on their new drug. If they're switching to fingolimod, they're, of course, going to need to do all the prescreening.