Novel Management Strategies for MS Relapse

Stephen Krieger, MD: To go back to what Dr Berger also brought up as a second-line strategy, if steroids can’t be used or steroids have been suboptimal, there is ACTH [adrenocorticotropic hormone]. Sam, maybe you can tell us a little bit about how and when you use that strategy for patients.

Samuel F. Hunter, MD, PhD: Well, this is a very interesting medical history issue, because ACTH was the first drug that was approved for using MS [multiple sclerosis] relapses and is currently only marketed in 1 form, and that’s a repository injection. The problem is, steroids are actually used in low doses, the 1 mg/kg doses. And it’s 1 of the first evidence-based things we had in MS that’s worse than doing nothing. They either need to get high doses of steroids or some other effective treatment. We have only 1 other effective treatment that’s a frontline relapsed treatment. We have plasma exchange, which everybody pretty much uses for really refractory situations. And if you have somebody who you think needs plasma exchange, you better start thinking, do they really have NMO [neuromyelitis optica] rather than MS?

So when you get to saying, “How do you do with steroids,” to a patient, because you said, “I need to treat this relapse,” and somebody in the room starts shaking their head like this, it’s often a family member because they’ve had such bad experiences. And these experiences range from your frank psychoses to not sleeping for a week to hospitalizations for some problem. Or sometimes really trivial things like people who develop neuropathic pain as a temporary problem after relapses. Those aren’t as big. But you have these kinds of events that have often occurred more than once. And once in a while it’s 1 of these things: “Steroids never worked for me.” And they’re very emphatic about it. You looked at your records and you say, “Boy, that sure is the case,” and you’ve got to decide how to treat them. And oral steroids are going to generally have the same liabilities.

Now when it comes to diabetes, anybody who has had a blood sugar over 300 mg/dL needs a good management plan from the affiliated primary care people on how to manage that because you shouldn’t be giving people steroids or ACTH. If they have really bad uncontrolled blood sugars, usually the diet is a problem as well.

I don’t think that corticotropin is a great solution for people with really fragile diabetes. But it’s a very good solution traditionally for people who have the psychiatric complications that are very disturbing, and for that tiny amount of people who really are refractory to whatever the effect of steroids are. And corticotropin is a different drug. The old concept was when they passed out the Nobel Prize, they passed it out both for hydrocortisone and for ACTH at the same time to the same people because they thought that it was basically the same thing. We now know that’s not the case.

The corticotropin works through a completely different messenger system in a completely different set of cells, although there are a small number of adrenal corticosteroids liberated, some of which are actually annoying like the mineralocorticoids. It’s fundamental—any inflammatory effect is very widespread on very many types of immune cells, without the same time to liabilities in the CNS [central nervous system] adverse effects for many people. And this is obvious to anyone who’s used the drug for a while. Many of us got that experience long before it was in its current form, and now that it’s a specialty drug, it makes it a little harder to get access. It’s also hard to get access promptly for many of these patients. But it has the advantage that it doesn’t require IV [intravenous] therapy as well.

And it’s been tested head-to-head. It’s 1 of the few things that’s been tested head-to-head against IV Solu-Medrol, and we have sound data that they’re both effective. And sometimes you have patients who exhibit a really clear preference for corticotropin. And they usually say things like, “It doesn’t make me feel nuts,” or, “It just works fast.” And they often phrase it in that way. There are very little scientific data to back up these claims.

Amy Perrin Ross, APN, MSN, CNRN, MSCN: I have a case example. A patient of mine who was a young woman had a fairly significant psychiatric history. But also when she would have a relapse, it was a bad 1. She was a hairdresser. And she’d had a relapse. We gave her some high-dose IV steroids, and then she insisted on an oral taper, which we gave her. But after about 4 days into the 5 days of steroids—she worked as a hairdresser, and 1 day a week she would volunteer at a senior citizen center—she went in and gave 3 elderly women buzz cuts before somebody stopped her and said, “Wait, wait, wait here. There’s an issue here.”

Stephen Krieger, MD: Why did they wait for her to do 3 times?

Amy Perrin Ross, APN, MSN, CNRN, MSCN: Three times. Well, the next time the relapse came around, we thought, “Oh, no, we’re not going there.” And so the adrenal corticotropin is something we tried on her, and thank heavens it was successful without the adverse events.

Stephen Krieger, MD: So that’s good. We think about access to care and the adverse effects and trying to choose the right relapsed strategy for the right patient. I think price also comes into effect here, so we think about the cost savings of oral steroids, as opposed to intravenous options, and think about the cost of having to admit someone to a hospital and trying to avoid that. We’ve put into the algorithm that you’re presenting here that cost matters when we think about relapsed treatment. And so there are different dollar signs for these treatments, with oral steroids being the least expensive and ACTH corticotropin being substantially more expensive. And then hospitalization for plasma exchange being very expensive and typically taking perhaps 10 days out of somebody’s normal life too if it has to be done in an inpatient setting. So we do want to think about cost as well as the data that we have for these strategies.

The last 1 to mention that out there in the community is the use of IVIG [intravenous immunoglobulin] for MS relapses, which is also very high cost and which I don’t think we have any good data that suggest it’s truly effective for MS relapses. I actually can’t think of a situation in which I’ve used IVIG for an MS relapse in recent years. I don’t know if any of you have but it’s used pretty, pretty rarely.

Samuel F. Hunter, MD, PhD: The data are basically collections of anecdotes, and I can’t think of any situation in which I’d use it. I guess if somebody needed treatment for plasma exchange, and you could not for some reason possibly use plasma exchange for them, but it’s a very hard drug to get. You can’t get it as an outpatient in any timely fashion. As an inpatient, you could probably get away with it, but somebody is going to have to pay for it someday.

I will say, I don’t believe from a pharmacology point of view that IV methylprednisolone and oral prednisone are the same drug. They’re very similar. You don’t get nearly the peak levels circulating. You’re not going to get the same penetration with oral amounts. But if it’s good enough, and the relapse isn’t critical enough, I see no harm in using such a safe strategy. But you have to take into account the GI comorbidities and the vascular comorbidities.

The reason you can get away with it in prednisone is because although it’s a mineral corticoid, the mineral corticoid effect pretty much tops out around 60 mg, and the rest of the 500 mg to 1,250 mg—depending on which variation you use, and I usually use lower ones—basically are looking at glucocorticoids. And it looks like it’s enough that it works most of the time. But there are lots of people who have very clear opinions about how well that works compared with the IV Solu-Medrol.

And you can cut down adverse effects. One of the principal management approaches with steroids, if it’s got adverse effects, is to give fewer days. And so I tend to use 3-day courses and see them back in a few weeks. If their relapse isn’t done, I do it again. If somebody is really sick, there’s no question they need 5. If they’re flat on their back, they may need 10. It’s just very situation-dependent on how you’re going to treat the patient.