AJMC®: What are the emerging challenges and opportunities associated with the rapidly expanding multiple sclerosis [MS] treatment spectrum?
Coyle: We currently have 23 distinct agents covering 10 mechanisms of action, so we have multiple options. In theory, that allows us to make an even better fit for the individual patient regarding their best disease modifying therapy [DMT]. It also requires a knowledge about all of these agents and understanding what each one offers, so the choice becomes more difficult. You would like people to be familiar with all the options, to have the ability to use those options and gain some experience with [them]. If the health care provider is not in an MS center, doesn’t really specialize in MS, or only has a small number of individuals with MS, it’s very hard to keep up [with] all of the choices. I think it’s wonderful that we have these complexities, but it also makes it more difficult to take full advantage and have an understanding of how they compare the pros and cons of each of the agents unless you see a lot of patients with MS and are taking care of MS on a very routine basis.
For folks who aren’t seeing patients with MS regularly, I think it would be very helpful to try to facilitate educational programs in MS. I think it’s important to make sure that all health care providers taking care of patients with MS are aware of the latest available agents and exactly what they do. Anything that can be done to facilitate health care providers being able to utilize the expertise of an MS center would be helpful. This could be through telehealth, for example. That sort of thing would be very welcome. In this era of COVID-19, we have seen how well telehealth can really work. Patients can be hours away and still have a meaningful interaction and educational session with an expert health care provider in MS. I think that will be increasingly utilized in the future.
AJMC®: Could you reflect on the pathophysiology of MS, particularly when it comes to new discoveries shaping treatment development and management strategies?
Coyle: There’s been a new emphasis in the past few years on B cells that appears to be a very successful way to treat MS. That became clear in the era of anti-CD20 agents. We know that MS is a neurodegenerative disease associated with injury to synapses, axons, and neurons from the earliest time point. That may be the important underlying feature for permanent disability and injury. We’re also realizing that there’s a tremendous benefit to following a wellness program to help the central nervous system [CNS] age well, which is important in the MS disease process because the central nervous system is under attack. We’re also realizing how important comorbid conditions are in a patient with MS—particularly vascular risk factors that are harmful to MS—and making sure they are optimally managed.
There is also a new emphasis on what we call innate immunity, which is non–B cell and non–T cell. Do we have penetrating agents that can affect the damaging process within the central nervous system? We’re increasingly understanding the importance of early treatment to get maximum benefit. We’re looking at the paradigm of how important it is to have highly efficacious treatment as opposed to an escalation strategy; this is currently under study. The pathophysiology of this disease seems to say that you want to treat it effectively very early.
Virtually all MS experts recognize that if someone has highly active MS with multiple prognostic indicators, they want to start with a high-efficacy agent from the beginning. Everyone would agree with that. The question is whether you can expand that more broadly, and it’s not totally clear yet whether vast majority of patients with MS would benefit from going on a high efficacy agent, even if they appear to have mild disease.
AJMC®: What are some of the considerations you would make when deciding on a treatment with a patient, with respect to both individual patient factors and drug factors?
Coyle: Broadly, people talk about drug disease and patient factors that are considered in choosing DMT. What is the efficacy? What is the safety? What pretesting do you need to do? What maintenance testing do you need to do? How is the DMT delivered? What is the dosing schedule, and how does it fit in with the patient’s lifestyle? There needs to be familiarity with the DMT to be able to counsel.
There are several questions to ask regarding the patient. Do they have comorbid conditions, and does that limit the choices? What is their lifestyle? What is their risk tolerance? Are they looking at pregnancy in the future, and how significant is that when making a diagnosis because a woman of childbearing age is your prototypic patient with MS? What are their expectations from a disease modifying therapy? Regarding disease factors, how bad is their MS? Do they have very active disease? Do they have a poor prognostic profile? Are you very worried about them, or do they seem to have very mild disease? These are all factors that would be key determinants in coming up with recommendations for their best DMT.
It’s unfortunate that access and economic factors related to drug tiering also enter into consideration; I think these are factors that are extremely artificial and really shouldn’t come into play, but they do, unfortunately. When you force choices, I think that’s suboptimal. If you’re going to do that, then you should be doing it on a class agent. For example, there should absolutely be access to a high-efficacy agent in a treatment-naïve individual. Our understanding of MS clearly justifies that. If that’s not the case, then there is something wrong with that tiering. Health care providers don’t like to have limitations on what they’re doing, but if you make a logical argument and offer comparable availability of agents, then it’s hard to argue with that logic. Where you can argue is where a tiering system may be completely illogical.
AJMC®: What is the importance of individualized care in the treatment of patients with MS?
Coyle: No 2 patients with MS are alike. One of the key features of MS is its great variability. This is not a stereotypic disease; it’s quite variable, which is important to keep in mind. We are now pushing personalized medicine, which is really the best approach to MS. We’re not at precision medicine yet for MS, though hopefully that will be coming. We don’t have meaningful genetic and other biomarkers to help us choose the best agent. I also think we can learn from group analysis, so I’m not saying that’s a bad thing. One on one, when that individual patient is sitting in the office in front of you, there will be issues coming up that are unique to that patient, that are completely different from any other patient with MS. That is the art of medicine. What you want to do is the best possible job for that individual patient. We really believe in the concept of personalized medicine now, and, hopefully, in the future, precision medicine. At the end of the day, it’s the individual choice for that patient.
AJMC®: How important is shared decision-making in the process of MS treatment?
Coyle: Shared decision-making is a fundamental principle in the treatment of MS that has been endorsed by every expert consensus group. The treatment of MS with DMTs is invisible treatment. The patient goes on treatment, and they really don’t necessarily feel better. DMTs are not treating symptoms, and the patient is not really meant to improve or get better. The purpose of DMTs is to minimize future events that patient has not experienced. It’s very important that the patient understands that and has realistic expectations, and clinicians should educate them about DMTs and their expectations for therapy. There are some patients who say, “Tell me what to do; you’re the expert.” That’s fine, but you really want to elicit from them certain properties that can help you make the best decision. I tell my patients about the importance of understanding this disease. Education is power. It’s our responsibility to educate the patient and put it in terms they can understand, so they can really be a partner buying into their treatment regimen and we optimize adherence. The treatment decision is so important that the American Academy of Neurology noted in its practice guidelines in 2018 that the discussion about the DMT should be a separate visit.
AJMC®: How would you assess efforts by payers to support shared decision-making, and how can clinicians and payers work together to select appropriate regimens and optimize outcomes for patients?
Coyle: There is such a wide spread of third-party payers. Some offer educational programs and reimbursement plans that are logical, and others do not. For example, it doesn’t make sense that patients with primary progressive MS, where there is only 1 agent approved, still need to go through 2 DMTs, both of which have had failed trials in that subtype before getting to the approved agent. That’s why it is so important to understand the disease in order to implement the appropriate tiering system.
With 23 options, I can’t argue if you begin to tier between classes. I don’t like it, but I can see the logic. There should be logic to all the choices, though. It’s important that payers interface with those with clinical expertise to gain a deeper understanding of these agents and ensure that treatments are given that are in the best interest of the patient.
In terms of building better relationships between clinicians and payers, I would recommend a seminar to review the latest thinking in MS and use of DMTs—pros and cons, etc—that third-party payers across the board could attend; it could be a virtual meeting for those making decisions about DMTs to get an education regarding questions and controversies. A panel of experts could put on a program on an annual basis if you wanted to get updates. Physicians and payers could work together on this; it doesn’t have to come from one side. You essentially want to make sure that you are hearing from true thought leaders, and you could be very honest about areas of controversy. That could be meaningful; people could bring questions to the table. For payers in which MS makes up a significant part of their business, this would be very valuable. Additionally, imagine if you could do an educational program where you could make suggestions, and people could buy into and endorse it; that would be viewed as a wonderful benefit in the MS physician community.
AJMC®: What are the most significant unmet needs in MS care, and how do you think those needs can and will be addressed over the next several years?
Coyle: We need better treatments for progressive forms of disease. They would probably have to be used very early in the disease process. We need to get CNS repair strategies; this is pertinent to not only MS, but virtually all major neurologic disorders. There are trials ongoing. We would love to have an effective paradigm that tells us the best mechanism of action to use in a particular individual and can quickly tell if they are responding or not. It would be wonderful if we had biomarkers of best DMTs to pick for them, and we could get very early feedback.