Q: How do you individualize treatment when managing patients with MS? 

What is the patient’s stage of disease? That is the first question to be addressed. There would likely be consensus that a patient who has a large disease burden (eg, gadolinium-enhanced lesions, new-onset disease, spinal cord lesions) should start treatment with 1 of the more effective therapies, such as ocrelizumab, natalizumab, or alemtuzumab.

The most important aspect of individualizing therapy is understanding the patient in terms of his or her treatment goals. A major issue that we face is providing the best treatment options to young women who develop MS and who would like to have children. Therapy for these women should be tailored around childbearing. For a patient who is planning on becoming pregnant and has mild disease (a few lesions and numbness), I might start treatment with glatiramer acetate, which can be taken during pregnancy.

One also wants to aggressively treat an individual with major risk factors, such as a patient who is male, or African American, or has multiple lesions. I would not stop treating a patient with interferon beta if he or she has been on it for some time, is doing well, and has not developed new gadolinium-enhanced lesions or new lesions or events. The really interesting question revolves around determining the best approach for patients with radiologically isolated syndrome. These individuals are asymptomatic, but have clear MS-looking lesions and on spinal tap there is inflammation or increased immunoglobulin. Those are the patients we should be screening and giving a lot of thought about how they should best be managed. As I previously said, we are having discussions in various ways about starting ocrelizumab for a 1-year period, then stopping the drug and monitoring the patient for immunological and radiological changes.

It is a step-wise approach and it depends on the patient, as Dr Hafler said. If you have a patient who is a young woman with modest disease and who wants to become pregnant, then you are going to use a drug such as glatiramer acetate. Otherwise, if you have a male African American patient with very active disease, the best starting treatment option might be ocrelizumab or alemtuzumab because you know that his disease is going to progress very quickly. Ultimately, the best treatment option for any patient depends on the patient. For example, a patient with a relatively low or modest burden of disease who has had 1 nonserious attack could have treatment options based on his or her preferences. Some patients may be reluctant to take injections even if the injectable drug has been around for a long time, has a good safety profile, and can easily be discontinued. Or maybe the patient does not want to deal with the potential side effects of certain drugs. With regard to radiologically isolated syndrome, the data show that approximately 40% of those patients’ disease will progress to clinical MS within 2 or 3 years. Therefore, my approach for those individuals, whether you go with an aggressive approach or even a step-wise approach, is to start therapy, particularly if they have at least 1 enhancing lesion, which means that they have MS without symptoms (lesions separated in time and space). I would start those patients on high-dose interferon, fingolimod, or natalizumab for a short period of time, stabilize them, and then go back to an immunomodulator, but not an immunosuppressive or immunoablative therapy.

We would certainly like to move toward true personalized, or individualized, treatment decisions guided by biomarkers. Ideally, we would have biomarkers that would predict outcome and guide treatment, and, if they change, they would allow us to have actionable outcomes such as changing therapy. We do not have all of those tools available to us at the moment.

I individualize treatment by looking at each individual person’s clinical course of disease. For example, I take into consideration how many relapses they have had, how severe those relapses have been, how well they recover from individual relapses—which is a particularly important marker—their neurological examination, and the regions of the nervous system that are affected. So, for example, I would favor more aggressive therapy for patients who have early cognitive dysfunction or cerebellar or spinal cord disease. I also use magnetic resonance imaging scans to influence my thinking about treatment selection, considering the burden of lesions and whether a patient has visible atrophy or the presence of a significant number of T1 black holes—all of those markers associated with disability. And, finally, I consider the individual patient’s characteristics, such as his or her own preferences about treatments, his or her tolerance for taking on risk, specific side effects that he or she would like to avoid, what he or she is trying to achieve with treatment, and whether there are specific factors (eg, family planning, timing of potential conception of children if that is imminent for the patient) that influence the type and timing of treatment. I put all of those factors together and, in a shared decision model with the patient, we come up with an initial treatment approach. We then outline how we would provide ongoing surveillance of the disease to determine whether that initial treatment selection was successful or adequate or if we need to change therapy.