Fred D. Lublin, MD: It's very important, once you start someone on a therapy, to monitor their response to it. There are several steps to that. We obtain MRI [magnetic resonance imaging] scans 3 months after someone starts on a disease-modifying therapy. Some of my colleagues prefer to wait 6 months to give the drug more time to run in, but that scan becomes the baseline scan for which we then assess the therapeutic response moving on. We'll do an annual MRI after that.
One monitors for both clinical attacks and MRI activity. We have not yet developed metrics to say that if you have 1 new lesion after 1 year, or 3 lesions after 2 years, or something else, that's an indication to switch. We don't yet know what the threshold is for saying that a drug is having an inadequate response. While we like to have individuals with no activity whatsoever, clinical or MRI, that's not necessarily the reality with the drugs we're dealing with.
We're also thinking about monitoring more closely with other metrics, such as ocular coherence tomography and cognitive function. We’ve now started doing cognitive testing on all of our patients on an annual basis to see if that gives us a signal to tell us that someone is moving along or not doing well.
Robert J. Fox, MD: Once a patient has been on an MS [multiple sclerosis] therapy for 6 or 12 months, or even longer, we're faced with a question: Is it working, and should we continue it? Really, there are 3 main ways we are looking at it. We're looking at it from an efficacy point of view. What's happened with the patient's relapse, and what's happened with the new lesions on MRI?
Ideally, the patient has had no clinical relapses, and has had no new or active lesions, or enlarging lesions on their MRI. We do use MRI to guide therapy, because it becomes a more sensitive measure of the disease activity than just clinical relapse alone. We don't ignore relapses, but we use the MRI to augment our understanding of the disease activity and what the therapy is doing.
Ideally, we want no relapses, and we want no new lesions on MRI or active lesions on a gadolinium-enhanced MRI. Where we exactly say 1 is too many, whether it’s 1 lesion or 1 relapse, is a judgment call. It depends on how severe the relapse is, how much residual deficit there is, and what the patient's tolerance is for an additional new drug that may have more risks associated with it. Then also, it’s the same for MRI. How many new lesions are there? How large is the lesion? How damaging does the lesion look to be, or lesions, on MRI?
The third part of considering a therapy is looking at how a patient is tolerating it. Patients may have adverse effects. They may not like the administration. For example, an injection. There may be safety concerns. A patient on natalizumab may have developed seropositivity for the JC [John Cunningham] virus and, thereby, has an increased risk of the brain infection PML [progressive multifocal leukoencephalopathy]. By looking at adverse effects and risk profile, we can make some decisions as to whether we recommend the patient stay on that therapy or move to a different therapy.
When choosing the next therapy, it depends on why we're moving from the first therapy. If we're moving from the first therapy because of a safety concern or an adverse effect, we might think of moving laterally, like from one oral therapy to another therapy. If it's because of disease activity, either clinical relapses or new or active lesions on MRI, we will generally move up in regard to the intensity of the therapy—from an injection therapy to an oral therapy, or from an oral therapy up to an infusion monoclonal antibody therapy.