Host – Dan Keller
Hello, and welcome to Episode Eighty-five of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller.
Many MS patients will require a change of drug therapy over the course of their disease, possibly because of relapse or tolerability. At last fall's ECTRIMS conference in Barcelona, I spoke with Eva Havrdová MD PhD, professor of neurology and head of the MS Center at Charles University in Prague, Czech Republic, about when and how to change therapy. I first asked her how she detects a need to change therapy because of a suboptimal response.
Interviewee – Eva Havrdová
It's very difficult to find the right solution for each patient, but as to our opinion, the best thing is to really start early treatment and monitor closely the patient. It means that you look not only at relapses or progression. It's too late. We also look at MRI after six months after starting treatment. And I think it is now quite proven that, if the patient has either relapse or new MRI activity, the response in the first year is suboptimal and the treatment should be already changed.
Interviewer – Dan Keller
So you have a very high suspicion?
Yes, definitely very high suspicion. And you can add some quality of life measures. You can add cognitive measures. You can ask the patient, what’s the level of fatigue. And of course, all this together brings you to the solution to change the treatment.
Do you generally find that you will pick something sooner on MRI then by patient report?
Yes, of course, because the events on MRI occur 10 times more frequently. But on the other hand, as to regulations for reimbursement, I cannot change the treatment just based on MRI in our country. So definitely in the future, this will be an option. But we need more data to prove to the sick fund that it's really worth doing it because if you do these changes and find optimal treatment for patients early, then the patient stays at work, and of course, the cost effectiveness of the drugs increases.
I suppose that depends on having a unified system, which is not built into silos. You know, when you get one payer here and one payer there; they don't care what's coming out of the other guy's pocket.
Yeah, yeah, of course. It's very difficult; and therefore, I think we need guidelines. And one of the ECTRIMS activities is to start working on some guidelines, and I hope next year we will have it.
So what do you do when you find something that would raise your suspicion or prompt you to do something different?
We monitor the patient even more closely, in three-month intervals. And very often we see that the patient develops a relapse after some MRI activity occurs. So we can change the treatment.
Do you often escalate the present drug? Or switch drugs immediately?
We have to start with injectables in our country, not with oral drugs, which is the mainstream now in other countries. And we hope we will also push our authorities to this strand because patients, of course, want orals. On the other hand, the safety of injectables is well-proven for more than 20 years. So for those especially who want to get pregnant, the safety is number one. And we try to switch as early as possible, because if another relapse comes, the relapse may be disabling, and we are just losing time in the brain of the patient. And as you know, here at ECTRIMS, the one day before, the health of brain was promoted in MS. And we would like to stick to this idea.
So it sounds like you change drugs, not escalate the present drug?
The escalation means the change as well. So we try not to switch within the first line, but we want to see more effect. Just because of intolerability or some known adherence of patient on injectables, we can switch within the line if there is no activity of the disease itself. Or if there are neutralizing antibodies on interferon, we can switch to Copaxone. But on the other hand, it was now published, based on data in MS base, which is a big registry of real world data, that it's really worth escalating to the higher efficacy drugs because you can reach much better effect.
Over the years, do most patients require some change?
Most of them do, though there are patients who are completely stable and not developing higher EDSS steps on injectables, but it's less than 25% of them.
Is there any way to generalize and say what the time course is? Or is it so variable?
No, it's very variable. And we do not know if it is based just on genes or on environment or lifestyle changes the patient is willing to undertake. We do not know yet.
So I don't know if you can generalize because each country is different, but do you have some scheme or algorithm in mind about how you would escalate therapy?
The problem is if the patient is not responding to the second line or higher efficacy therapy, because we then have to switch within that line. And we do not know if he doesn't respond to anything we have. We do not know what to do. So we cannot switch or jump from one treatment to the other after six months of treatment, because you have to allow the treatment to have an effect. So at least six or nine months is okay. If the patient is not responding, then you can jump to other treatment. But hopefully the patient will respond to the third or fourth treatment, because it's not without limitations.
Is combination therapy every indicated?
Not yet. I have thought many years ago that neurologists are just reluctant to use combination therapies, but now there were some trials, and it's not showing that effect. So it's not like in oncology. Though the principle is so clear, that you can combine drugs with various mechanisms of action decrease, some side effects, and increase the efficacy. Oncologists do that. We don't have drugs in the multiple sclerosis with this potential yet.
Right. In hypertension they've just assumed they're always going to have two or three drugs, and same thing now with diabetes and things like that. But I guess this would be a big conceptual breakthrough for neurologists?
Yeah, and doesn't seem to be today's issue.
What has been tried in combination?
The first combination which was tried was natalizumab and interferon. And it seems that it didn't work. And then, of course, it was also a small trial, natalizumab plus glatiramer acetate, and nothing just to safety was, of course, seen that. And some others, but nothing really.
When there's an acute exacerbation, do you overlap steroids with the ongoing drug?
Yes, of course. Yes. It was proven that it's safe, and it's okay.
So there is a combination, but short-term?
Yeah, it's a short-term combination. And definitely it helps because all the underlying immunomodulating drugs do not work against the acute relapse.
What have we missed or is important to add on the topic?
I think that neurologists have to be aware, and of course, pharmacovigilent. You have to know the mechanism of action of the drug; you have to know the adverse events possible and how to prevent them—how to monitor the patient to be safe.
Thank you for listening to Episode Eighty-five of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations.
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For Multiple Sclerosis Discovery, I'm Dan Keller.