Appropriateness for Induction Therapy in MS

Fred D. Lublin, MD: So when we get into individuals who are meeting your threshold to say “treat,” there are a couple of schools of thought as to what to do next. It’s not just to treat or not to treat, but once the decision to treat is there, at whatever point, and we pretty much all agree earlier is better, then there is this strategy of: do you start with something safer and escalate, or do you hit them up-front hard with something more aggressive and potentially less safe and then consider what to do later? So the one has been called induction, but almost no one is doing true induction therapy, which would be to hit someone with a therapy that knocks out the immune system, and then, down the road come to something safer, right?

So induce an immune halt to the disease and then come up with something long-term, safer. And that’s not really been discussed very much, even though people talk about induction. It really is highly active to start, or escalation with something that is safer and that we know works. And that’s been one of the big debates out there for which there’s precious little data but lots of opinions. So we’re going to get some opinions here as well as to where you stand on this. Let’s start with you, Tom.

Thomas P. Leist, MD, PhD: I do think that early on there is a window of opportunity, particularly in patients that present with higher-risk disease—so patients, for example, that have incomplete recovery from an initial attack, or patients that have numerous lesions at the time of the initial presentation. So for patients that have characteristics that are more concerning, I tend to go towards the higher efficacy medications. Naturally, where we speak in the United States, very often my choices are not necessarily level, so I have to deal with the formularies of the insurance companies. And so, there is a compromise between where I would like to go with an individual patient based on the data that I mentioned before and what I can actually do.

Suhayl S. Dhib-Jalbut, MD: I agree with what Tom said. And in addition to that, I would also take into consideration the location of the lesions, brain stem, spinal cord, bladder dysfunction. If spinal fluid results are available, the number of oligoclonal bands might be a predictor of a worse prognosis. And the third thing is race and ethnicity. African Americans might not respond as well to conventional modest efficacy drugs as the rest of the population. So I take all these factors into consideration.

Fred D. Lublin, MD: Pat?

Patricia K. Coyle, MD: Right now I think it’s critically important to treat early, to make sure our patients are following a wellness program, and to make sure that any comorbid conditions are being optimally managed. We do not yet have data that say that when starting a high efficacy agent in everybody, they’re going to do better. We simply don’t have that data. We’re clearly using shared decision-making. I totally agree that if somebody has very active disease and a bad prognostic profile, efficacy becomes important to me, and I’m going to counsel and discuss with the shared decision-making with the individual that it may be very important to pick a high efficacy agent.

Otherwise, if that’s not the case, then I think there are other needs and considerations that you have with the patient, but then also critically important is to follow them closely, particularly for the first 2 years. If there is unacceptable breakthrough activity, you can make a switch.

Fred D. Lublin, MD: OK, James?

James M. Stankiewicz, MD: I come at this from a little bit of a different perspective, which is that I think a brain MRI [magnetic resonance imaging] is only so good. It’s only so sensitive. And there is a lot underneath the surface that we don’t really see, and we know when we use novel research techniques that we can see ongoing damage that we can’t see otherwise. I also think that any inflammation in the brain potentially can come back and haunt someone, maybe not immediately but may catch up with someone 15, 20 years later. So I think it’s crucially important to prevent inflammation. And I think that we have the data. We know that some of these drugs do better at this than others.

Now it is fair to say that not every patient necessarily will need a stronger agent. Some will get by over the long term doing better on a lower efficacy agent. But I also think that it’s hard to really necessarily predict, actually. When you really look at demographic factors and some of the other things that we use and you study this carefully, I don’t think we have a great barometer about how people are going to do. And I think if you want to wait to see, you may be a little behind the curve already.

And I also would say that I think the profiles of the treatments are changing too. I think we come from a place conceptually where, years ago, the drugs that were more potent had more problems in the way of adverse effects. So, higher risk. And I don’t know that I necessarily think that’s as true anymore. I think that there are certain drugs for which the safety risk, the tolerability, is within an acceptable range so that we can use it sooner, insurance permitting.

Fred D. Lublin, MD: Clyde?

Clyde E. Markowitz, MD: I have been a big proponent of the shared decision-making conversation. Find out what the patient’s concerns are, what my concerns are, and kind of mesh what we think is the right approach. But I have found that I’m becoming much more aggressive earlier than I used to be, and I think that’s driven by the idea that you see patients over years. Even though there’s not really much change on the MRI scan, they are having a slow dwindle in their world. And I wonder whether we should be much more aggressive earlier? There’s some data, not a lot, but some data that suggest that if we really oblate the immune system up front, you can really put the disease in remission, in essence. For how long is questionable. And then ultimately it becomes a safety question, right?

We would all be in this conversation if there weren’t some safety concerns to worry about. And I’m struggling with the idea that I’m balancing safety with what the disease might look like over time. And it’s not an easy place where we live right now. So clearly we need more data to support this aggressive induction approach, like the oncologists do and they basically can dial things back. Or even as rheumatology does, to some degree. So I’ve been moving more into that arena. As James pointed out, you don’t see everything on an MRI scan, and I really think there’s smoldering disease activity that’s happening that we’re not picking up, and we need to do something. The other side to that is, how do we do it safely and not cause any major problems?