Ryan Haumschild, PharmD, MS, MBA: It’s creating those pathways too that might be unique for a patient. They might be better off immediately jumping to one therapy that normally maybe you might bring in later because of cost or because of access issues. But if it will provide the best benefit for them, and they can stay adherent, how do we consider that? I think another example is, there are studies out there demonstrating that early initiation of disease-modifying therapies is important rather than delaying treatment. Dr Hickman, I know you deal a lot with this too as you’re evaluating therapeutic plans and coming up with unique treatment pathways. If you could, for our viewing audience maybe expand upon how have the studies demonstrated improvement regarding early initiation, and what has that meant for patients in treatment pathways moving forward?

Amanda Hickman, PharmD, MPH, MSCS: To extrapolate from what you were saying, the guidelines say patient-centered over and over again because if the patients are not adherent to their medications, they are not going to work. I often tell patients, “This medication is going to work if you believe in it, and your belief is bringing 60% of efficacy to it.” We need them to take it, and we need to match it to them to make sure. Maybe they’re really busy, and they are not going to remember to take something once a day or twice a day. So, we’ve got to look at something that’s a little less frequent. Or they are not tolerant to adverse effects at all, or they don’t want their immune system messed with. Definitely we need to do that. But the other thing that the guidelines say over and over again is early treatment.

There are definitely studies out there where if a patient starts their DMT, or disease-modifying therapy, before their second relapse, they have less of a chance of severe disability. So, getting that medication started as fast as possible [is important]. From diagnosis to getting started we have a lot to achieve. There are even studies out there saying that it could take up to 18 months from the first office visit, and this is not necessarily with a neurologist, this is them noticing they have symptoms and seeing their PCP [primary care physician] potentially, to getting on their treatment. That’s a long time to go. We’ll touch on this a bit later, but in some of the studies we’ll review, some of them only looked at patients for 6 months, and every group had relapses within that 6 months. Time is definitely not on our side when we’re wanting to spend the time with a patient and make sure they are confident in the treatment and regimen plans. But get them started on it as fast as possible.

Ryan Haumschild, PharmD, MS, MBA: It’s such an innovative thought too because the time to treatment we know is important, but we used to have this antiquated approach of, we’re going to reserve that for later lines of therapy. But even sometimes if it’s more costly, if you can insert that earlier, and get a better, deeper, more durable response, you’re actually saving costs in the long run when you think about the total cost of care and providing great benefit to the patient. And as you said, instead of having them go through that relapsing portion of their disease, you can get [started] earlier and reduce that. That’s going to improve quality of life, and I think that was really impactful.

Amanda Hickman, PharmD, MPH, MSCS: Absolutely.

Ryan Haumschild, PharmD, MS, MBA: When we were talking about early initiation of therapy, I think it’s important that we talk about frontline therapy. Dr Williams, you deal with a lot of patients and you have a lot of experience in this area. In your experience, which agents do you typically utilize for first-line therapy in your practice?

Mitzi Joi Williams, MD FAAN: How we approach MS [multiple sclerosis] therapy has shifted over the past decade or so. Traditionally, the majority of us in practice had done escalation therapy. Meaning, we start with medications with fewer adverse effects but that may have less efficacy as well. Then if a patient has a problem, we shift to a higher efficacy, we pull out our big guns, so to speak. But now there’s a shift of starting high-efficacy therapy early because there are many studies that suggest we can do a better job of preventing long-term disability, as you alluded to, if we start with very high-efficacy therapy. Then if we need to de-escalate later, we do that. The first 5 years of disease is when we have that opportunity to make a huge impact on how people do in the long term. So, what we do in those first couple of years, and as you said sometimes they don’t get to us until they’re almost 2 years into the onset of symptoms, we have the opportunity to make a big impact.

So, I often use high-efficacy therapies. I use monoclonal antibodies in first-line [treatment]. I often may use immune reconstitution therapies [in the] first line. I do use some of our traditional therapies, not quite so much, but usually oral and intravenous treatments, if I can get them in the first line, I try to do high efficacy. I explain that rationale to patients, and they understand that. Again, it is that shared decision-making, sitting down with them, explaining, and many of them are very amenable even though those therapies have a higher risk, to try to stop their disease as early as possible.

Ryan Haumschild, PharmD, MS, MBA: I appreciate the examples, the different classes. And hopefully, over time, we’re going to expand that opportunity for patients so that we even have more target agents in the frontline setting, longer durable responses, and I think ultimately, providing more of a holistic advantage there. Thank you for going through that. I do want to come back to you though because there’s always a trade-off with many MS agents related to their safety and efficacy. As I evaluate different treatments either for pharmacy and therapeutic inclusion or even for sequencing, I think that’s something we always look at, what’s best for the patient from an efficacy standpoint and safety. But how do you weigh this trade-off? How do you look at most agents that are considered when you’re evaluating safety and efficacy? Are there some where the efficacy is more important, or for some you’re thinking, regarding the safety, if this patient has the chance to abandon treatment, I’d rather not go that route? Talk me through that a bit. I know it’s patient-specific but….

Mitzi Joi Williams, MD FAAN: Yes, absolutely. There are some high-efficacy therapies, some monoclonal antibodies that require a great deal of monitoring. And, although they may have very good efficacy, if there is concern that my patients may not be able to keep up with several years of continuous monitoring, even though it theoretically may seem like the best thing, in the long run, that may not be the best option for that patient. I do not downplay adverse effects. I do try to explain them as thoroughly as possible, and I do talk about, again, the real-world data. I talk a lot about the data with my patients, I tell them numbers and percentages. Compared to the general population, what is the risk of this malignancy, and then what was the risk in this trial? I draw graphs and graphics and things like that. I try to go over the data with them so they understand to the best of their ability. And again, oftentimes, even though there may be potentially serious adverse effects, they’re usually very rare.

The other thing I think is key is that with MS therapies, although many of them are classified more like chemotherapeutic agents or depleting agents, we’re not giving them with the intent to deplete the immune system as we would if someone had a malignancy. I think that nuance is very important for us to point out. We’re depleting, but not completely depleting. People are able to go about their daily lives. I always talk about life prepandemic, when we weren’t asking people to wear masks with these medicines. I try to explain that as plainly as possible without downplaying the risk. Oftentimes, patients again are very amenable to high-efficacy therapy despite the risk, which is usually small, of some of those more severe adverse effects.

Amanda Montague, Ed.M: Another thing, if I could add, that I think is so important in terms of the shared decision-making with patients is to help patients understand the risk of the natural progression of MS because that often gets missed in these conversations. We’re so focused on the risks that some of these therapies carry, but there is a real risk to the natural progression of MS that can help contextualize for people living with MS, the choices they’re making in those treatment decisions.

Mitzi Joi Williams, MD FAAN: Right.

Amanda Hickman, PharmD, MPH, MSCS: We went from an age of providers saying, “when you end up in a wheelchair,” to, “We’re going to try to keep you as normal as we can. We’re going to keep you at this baseline as long as we can.”

Transcript edited for clarity.