First-Line Therapies for Relapsing Multiple Sclerosis

Fred Lublin, MD: Let’s move on to our next segment. Our next segment is first-line therapies for relapsing MS [multiple sclerosis]. Patricia, why don’t you start out with the concept of first-line therapies and whether that’s a reasonable concept to continue?

Patricia K. Coyle, MD: I don’t like the concept of first line, second line, third line. We should be able to use any agent that we feel is the best choice in our patient initially. Now, that having been said, what are first-line treatments? Well, obviously the injectables, the varieties of glatiramer acetate and interferon-beta. With regard to the orals, I consider every oral but cladribine to be a first-line agent. That’s the natural spot to use an oral. Why is cladribine not listed? Well, in the label that cladribine got in the United States, they did not recommend using it in a patient with a first attack. I think it could be, but that’s bending the curve a little. Then when we go to the infusibles, monoclonal antibodies. I think they’re all first line with the exception of mitoxantrone, which we basically never use in the United States, and alemtuzumab, which has been recommended in the US label as a third-line agent. I feel very comfortable using the orals, using several of the monoclonals and infusibles, and certainly the injectables as “first-line agents.”

Sven Meuth, MD, PhD: I cannot agree more. I would like to support your concept that we should be free as physicians to decide which agent we are using in a given patient. However, I have to say as an MS center, as a university hospital, we at the University of Münster are a little bit free to have a certain concept. However, when it comes to reimbursement, the office-based neurologists are not allowed to go on these treatments, and this is why we are a little bit limited, based on this reimbursement situation. From the pathophysiology behind it, I cannot agree more. If we have a given patient with a highly active disease, we should not play around with something like platform therapies, but we should be able to start with a monoclonal, for instance.

Fred Lublin, MD: When you say they’re limited, the clinicians out in the community, what can they start with?

Sven Meuth, MD, PhD: If it’s really a highly active patient demonstrating more than 9 T2 lesions in the MRI, and more than 2 relapses with an EDSS [Expanded Disability Status Scale] progression, they are allowed to start right away with a highly active agent. We have 1 difference here in Europe compared to the United States, and this is the approval of fingolimod, which is, in our country, approved as an agent only for highly active patients, while it’s in your spectrum of regular, or of first-line therapies, if I recall correctly. This is a difference, and this brings me to the approval of new sphingosine 1-phosphate modulators. But in the majority of patients, we have to start with platform therapy or first-line therapy, and then we can have this escalation concept, and this is, in my opinion, not the way to go.

Fred Lublin, MD: Are any of the orals in your first lines?

Sven Meuth, MD, PhD: Yes, dimethyl fumarate and teriflunomide are among the first-line therapies.

Fred Lublin, MD: Tell me again, what was the definition of highly active?

Sven Meuth, MD, PhD: Highly active should be if the patient is treatment naïve, then we are asking for 2 relapses leading to EDSS progression and a significant T2 load, normally defined as 9 or more lesions. And I think you will agree that this is far too late to quantify these patients as highly active.

Patricia K. Coyle, MD: Exactly.

Fred Lublin, MD: Wallace?

Wallace Brownlee, MBChB, PhD, FRACP: Yes, in practice in the United Kingdom, British neurologists are increasingly using early intensive therapy in patients with newly diagnosed relapsing MS. Until alemtuzumab was suspended by the European Medicines Agency last year and investigated in detail, we were using quite a lot of alemtuzumab first line at our center, the National Hospital for Neurology and Neurosurgery. Increasingly in the last year, that has been replaced by either using ocrelizumab, or in some patients, perhaps more like the ones that Sven described, cladribine also. We also have access to all of the oral medications first line with the exception of fingolimod.

Fred Lublin, MD: Why not fingolimod?

Wallace Brownlee, MBChB, PhD, FRACP: Fingolimod, like in Germany, is reserved for patients who are second line or very highly active, and that’s really on the basis of concerns around the time it was licensed over cardiac safety. While I must say with long-term clinical experience with this drug, that has become less of an issue, and it’s become clear that really that is a problem only with the first dose.

Fred Lublin, MD: What’s happened in Europe with alemtuzumab? Where you using that as first line?

Wallace Brownlee, MBChB, PhD, FRACP: We were using it first line, and we’ve still got the option of using it first line in people whose MS is taking a very aggressive course. Although, generally these days, we are mainly using it as a second- or later-line therapy in people who’ve continued to experience relapses and/or MRI activity on a first-line treatment.