Brenda L. Banwell, MD: Fingolimod is a tablet, 0.5 mg, given daily. The frequency of dosing is meant to be once per day. We monitor the white blood cell count and, very specifically, the lymphocyte count, which, coming back to my prior comment about how the medication works, lymphocytes are the immune cells I was referring to that are educated in the thymus and lymph nodes and, when turned on, are part of the culprits that contribute to attacks in multiple sclerosis [MS]. So we expect those numbers in the blood to go down. That’s how the medication works. But if the numbers go down too low, we often change the frequency of dosing. Instead of giving fingolimod daily, we may give it every second day. That’s common practice at this point, but I will mention that there’s still work to be done to determine if that’s the optimal way to manage the white blood cell count in patients treated with fingolimod. Protocols may change, in that regard, over the next few years as we learn more about fingolimod’s use in the real world outside of clinical trials.
Lauren B. Krupp, MD: The availability of an oral agent has made a huge difference. It also has brought to light how relatively ineffective the interferons were. Therefore, it has raised awareness that high efficacy, early efficacy treatment is a very advantageous approach. The benefit of preventing relapses, of preventing enhancement in terms of enhancing lesions, preventing new lesions, is so important in terms of the well-being of our patients. Some of that is immediate. Nobody wants to have a kid have to miss school because of a relapse. I believe what we’ll see is that some of that is also going to occur in the future. These kids are going to be doing better because you’re able to control the disease early on more effectively.
Brenda L. Banwell, MD: The approval of fingolimod has several implications. First of all, it has provided the first approved therapy for pediatric MS, enhancing the ability of physicians to prescribe a treatment and gain insurance authorizations and approval.
For patients who have been treated in pediatric MS programs in the United States for the last decade and a half, we have advocated pretty successfully with regulatory agents, more effectively with insurance payers, in terms of being able to prescribe different medications for our patients. In my practice, the approval of fingolimod has had a relatively modest effect on my ability to prescribe treatments that I think are appropriate for a given child. But that is, in part, because I work in a recognized pediatric MS center of excellence and have somewhat effective strategies to communicate with insurance payers to argue on behalf of my patients as to why they need particular treatments.
I think the approval of fingolimod will make that process easier for everyone, certainly if you’re prescribing fingolimod. I think the monitoring of patients being prescribed fingolimod is important. There’s a first dose effect, and you do need to give the first dose in a monitored setting, which, of course, means that a practitioner working in a more rural area or in a setting where they may not have the same facilities does need to link with regional facilities for adult MS to provide the same surveillance and safety when they initiate therapy.
Monitoring is very important. Whenever you prescribe a therapy, including something like fingolimod—which has some significant risks if not used appropriately—all providers need to be familiar with the monitoring for the use of fingolimod, which includes more than just measuring the blood counts. You also have to monitor retinal health. You have to have an eye exam. You have to monitor for skin changes that could be indicative of either infection or, potentially, malignancy, although we all think that would be quite uncommon in children.
If children and teens decide not to take fingolimod for more than a week, then, when they restart, they have to monitor it again. This is important, because teenagers, in particular, are notorious for deciding, often without sharing with anyone, that they might just skip a week. We have to warn them about the safety side of that.
Just because fingolimod is a tablet does not make it safer than other medications. And that’s a reminder I give every family. It looks like it is easier to take, but that doesn’t reduce the responsibility for monitoring its safety. And that’s something that we, as an entire community, need to be careful of.
We haven’t had a chance to talk about vaccinations, but it’s relevant to point out that before we start any therapy we need to review the vaccine history of our patient. We need to advocate that they complete the full regional advisory for the vaccines that they need in that world region. We want to be sure, in particular, that they have been vaccinated against chickenpox, which, if you acquire as an infection when you’re on a medication that reduces your immune system’s normal function, can be a much more serious infection.
We also need to keep in mind that [when a patient is] on certain medications, but not all, giving a vaccine is something that you need to think through carefully, because some of the medications we use, particularly in adults, but, in the future, in children, may alter how well a patient responds to a vaccine. If the vaccine does not generate the immune response that it was designed to generate, then the patient may not receive the full protection from the vaccine. And, of course, very importantly, for patients on many of the MS medications, live attenuated vaccines, a subset of different vaccines, are not advised.
So, again, this requires that all individuals who prescribe any of the MS medications need to be very well versed in the prescribing pattern of the medication, the ongoing safety surveillance for that therapy, and the pretreatment approach in terms of checking if the patient has received vaccines. For some of the medications, you need to be sure that the person does not have tuberculosis, and you need to be sure that you know about their hepatitis status, and particularly if they were vaccinated.
These are very, very important considerations that should not get lost in the prescribing process for any of these therapies.