New Treatment Landscape in MS — Preventing Long Term Disability Through High Efficacy Treatments in Early MS - Episode 3

Paradigm Shift in MS Management

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Experts in MS discuss the evolution in treatment options over time and the shift towards use of early high-efficacy therapy.

Neil Minkoff, MD: As someone who’s been involved in medication management, I feel as if the structure around MS [multiple sclerosis] management, or at least the paradigm around MS management, has changed pretty dramatically over the last, say, 15 years. There was the use of self-injected medications. Like we did with a lot of things, like hypertension—you start with a β-blocker, then you add an ACE [angiotensin-converting enzyme] inhibitor—it’s like progressive therapy. It feels like that paradigm has changed in MS. Dr Okuda, you could talk a little about that. You’ve been an advocate for early aggressive therapy for quite some time. Maybe you could talk about how you’ve helped change that paradigm away from incremental therapy to more aggressive early stage therapy.

Darin Okuda, MD: What may be important is to go back in history and understand why we had an escalation approach back in the day. It was because of the limited treatments we had. In 1993, we had Betaseron. Around that time, a patient had to win a lottery to receive treatment. I believe Avonex and Copaxone followed in 1996. In early 2000, you had Rebif, then the introduction of Tysabri, or natalizumab, and the entry of a variety of oral treatments. What has happened over the past 10 or 15 years is we’ve had a number of different treatments that have differing mechanisms of action. Science has advanced as well, highlighting how other cell types may be more important in the pathophysiology of multiple sclerosis. The availability of higher efficacy agents has had an effect. That list may vary. Some would put alemtuzumab, Tysabri, ocrelizumab, Mavenclad, and ofatumumab within that list, and may include or leave out Zeposia, fingolimod, and Mayzent. Then you have everything else.

Looking back on history, that’s all we had. All we knew was if things seemed worse, we would escalate you to an interferon-based therapy if you were on copolymer. Now, we have a wealth of treatments to choose from. The rationale for using a high efficacy treatment first is to allow for preservation of neuronal tissue. When an exacerbation occurs, if history is correct, an MRI relapse will outnumber a clinical relapse 10:1, and that’s a key marker in the no evidence of disease activity metric that has been created, whether or not we agree upon that as being a valuable tool. We see a lot more disease on MRI than clinical symptoms that represent exacerbations.

We embark on this high efficacy approach in an effort to prevent disease from happening, because we can’t take that away. If someone has optic neuritis or a bad spinal cord relapse, steroids do not improve their long-term outcome. It is what it is, and you hope that recovery is full. It’ll be dependent on race and ethnicity, as Dr Leist mentioned, and a whole variety of other factors. The philosophy of giving the best first appears to be a smart philosophy. It may not be the right philosophy in all cases, though, because there is risk of overtreating people. The risk to the system and the payer is missing a group of individuals who then have disease activity and progression in which they’re now pulling on resources that need to be covered by the payer because of inadequate disease management.

Neil Minkoff, MD: I want to pull Dr Ross in here, if I may, and talk about balancing patient concerns, coverage, determinations, the desire, and the paradigm changing to be more aggressive earlier based on what’s now available. You’re probably caught in the middle of that conversation quite a bit. How do you help balance those determinations between aggressive therapy and coverage determination? One of the things I took away from what Dr Okuda said was that the definition of high efficacy is not necessarily standardized. 

Nancy Ross, PharmD, BCACP, MSCS, CSP: Right.

Neil Minkoff, MD: Is that fair to say? How do you help people navigate through that?

Nancy Ross, PharmD, BCACP, MSCS, CSP: The troubling part is that not all of the payers have adjusted their preferred agents. They may still have the more traditional, older agents listed as preferred on their formulary. When you have a physician who wants to be aggressive early—maybe the patient has lesions in suspicious places, maybe they’re young, their ethnicity is higher risk, or it looks like they’re going to have advancing, progressing disease—and you want to start them on something that’s more high efficacy than your traditional Copaxone, or glatiramer acetate, trying to convince the payer that they need to go along with that and justifying your reasoning, when there are no national guidelines or anything that we have to argue one way or the other, can be challenging.

It can almost scare off a new patient when you’re telling them that you’re going to put them on an excellent medication that just came out that we have a lot of high hopes for and could keep them from getting worse in the long run, but they start getting scary letters from their insurance companies saying it’s not preferred and they want to switch to something else that’s cheaper. I have patients who will say to me, “But I want to save my insurance company money.” I’m like, “That’s very nice, but we need to do what’s good for you and make it work.” It can be quite challenging.

Transcript edited for clarity.