Kevin McKown, Rheumatologist and Academic Professor of Medicine, talks about the effects of scleroderma and a new clinical transplant that has become the treatment of choice for some of those most severely affected.
Let’s start by establishing the scleroderma problem. What is it and why is it so dire?
McKown: Scleroderma is an autoimmune disease meaning the body’s immune system attacks the body. It comes in different forms. There’s a skin form which tends to involve kids and then typically in adults there’s two forms that are systemic, meaning that it can involve the entire body. One is called limited cutaneous system sclerosis, which is a kind of a mouthful. We just call that limited scleroderma, and people who have that typically have a very slow disease progression, if it progresses, that can occur over years to decades. Then there’s a second form called diffuse disease or diffuse cutaneous systemic sclerosis. That has a much more explosive onset and typically people have severe involvement within just months to a year or two.
Is that what Chuck had?
McKown: Yeah.
His prognosis wasn’t very good.
McKown: That’s right. In order to be in the study, which proved that this autologous stem cell transplantation was effective, you had to have an estimated five-year survival of only 50 percent. Just for safety reasons, places that are doing this autologous stem cell transplant, which is now seen as standard of care for people with severe disease, still have to fit that same criteria.
To extrapolate that out, his life expectancy was very dire.
McKown: Yeah. He was in a bad place for sure.
What types of symptoms were happening with him that made it bad?
McKown: For most people, the biggest problem is the lungs are involved. You get inflammation and scarring in the lungs to the point where people have trouble breathing. They can very easily get infections, which can be fatal. Sometimes people will also get involvement in the heart, which can lead to fatal heart rhythms. Then some people also get kidney problems where the blood supply of the kidneys gets choked off. In response, the body tries to increase the blood pressure to try to get more blood into the kidneys, and that really high blood pressure can be fatal as well.
The other thing is he had run his course with whatever treatments were out there.
McKown: Right. We do have treatments that have been shown to, in some people, stabilize their lung disease. We don’t typically see a lot of improvement, but for a lot of people, we declare victory when that happens because the good news is with scleroderma, oftentimes if people can get through that first four or five years, then a lot of the scarring that occurs in the body tends to loosen up a little bit. If you get through the first four or five years, the chances of some new serious problem occurring get much smaller over time. If people get through that first four, five years, often they do much better.
But that wasn’t the case for him?
McKown: But that was not the case for him. He was getting worse despite the best therapies that we had to offer.
Then you decided that the best option for him was this clinical trial, right?
McKown: Actually, the clinical trial was a large, international North American study. 26 centers went over about 10 years just because it’s very hard to recruit for a number of reasons. The study really did something that we always hope for, but often don’t find, and that is the study really proved that this is a better way to go. For people in this situation, once the study results came out, it was pretty clear that this changed therapy, and this is something that was the treatment of choice for people who were in this dire situation.
Tell me about that process.
McKown: What happens is this would only be done in places where they do bone marrow transplants, and here at University of Wisconsin they’ve been doing them for decades. Basically, they take out a sample of people’s bone marrow and then they use radiation and chemotherapy to basically wipe out the person’s immune system. That’s why it’s so dangerous because then they’re very prone to infection at that point. There’s a process by which they try to remove the auto reactive immune cells, the cells that are causing autoimmune process, and then they infuse that back in and hope that the body will basically take up and graft that immune system. It’s the patient’s own immune system, just kind of cleaned up from what we think are the bad actors. But it’s that danger period right in there. In a previous European study, about 10 percent of people died in that process, which is why there was a high bar to get into the study. In the U.S. study, they’d made some adjustments and so it was only about 3 percent of people that actually died as a result of this process, which is still a risky process. Once people get through that, most people have done great. They’ve felt better. We’ve seen improvement in things like lung function. The vast majority of people are not going to take any sort of immune suppressant medicines anymore. The longer-term data shows that, for people going into the study, about 80 percent survival versus 50 percent survival. For the people actually got all the way through the protocol, it was closer to 90 percent survival versus about 50 percent. There was a big difference in both quality and quantity of life.
It really improves their life. For some of the people who are just on the medications before, they’re trying to just hold steady. For him, he says he’s 180 percent better. It’s a big turnaround.
McKown: It is. Even if you look at things like employment, there’s a big difference in people who are actually able to go back and do the things they want to do, whether that’s work or just enjoying life. It’s a big difference.
You’re the one that decided to bring this here. You became interested in it because of patients like him. How does it make you feel to have seen it before? You’ve seen patients who didn’t have this option, I’m sure, and now people like Chuck?
McKown: It is amazing. It really is. It’s so exciting to have someone who is desperately ill and then to have something like this to offer is just amazing.
Once, you ran out of the medicine. What else could you do?
McKown: There were a few people for whom lung transplantation could be considered. Many transplant centers don’t offer a transplant to these people because they do have problems in other areas of the body, which people worry are going to make them less suitable, less successful in terms of long-term outcomes. For most people, practically speaking, once they ran through conventional therapy, there really wasn’t much.
Is his prognosis going forward pretty good? Do you think he is cured? Is scleroderma something you have forever?
McKown: Yeah. That’s a really interesting question. One of the things that’s happened is that this has been so successful now, scientists have to go back and say what’s happened? Everybody kind of assumed or hoped that we were going to sort of reset the immune system, get rid of the bad actors, but we don’t know specifically why he got this disease in the first place. He’s still got the same DNA. Who knows what triggered it? It’s a rare disease, but it’s not a genetic disease. I think we can be optimistic. So far, the people who’ve been followed as far as ten years out, they don’t seem to be getting it back. We’ll have to maybe wait another 20, 30 years and have Chuck tell us how he’s doing.
Exactly. I love it. Going back to the process, it’s like rebooting his immune system.
McKown: Yes, that’s exactly right. That’s what people were saying. It’s like, this is a chance to try to reboot the immune system. I mentioned how this seems to be what we call a monophasic illness. It hits you hard. If you can get through that first four, five years, often people do okay if they haven’t had a lot of damage that first four or five years. That may be different than some other autoimmune diseases where it’s been looked at, for instance, in lupus. It doesn’t seem to have this long-term benefit for people with lupus or in another autoimmune diseases where this has been tried.
What are the concerns of doctors who are not doing this procedure, do you think? You touched on the fact that the procedure itself is a little risky.
McKown: Yeah. The only people who are doing this procedure would be transplant doctors. I don’t think any of them are particularly worried. This is something that there’s only going to be a very small number of people. Even the people with scleroderma, it’s only these people who really have a severe disease that seems to be worsening that are going to be candidates just because of the riskiness of the procedure.
The study is done. The clinical trials over. Who funded it?
McKown: It was actually funded by the NIH. In terms of organizing the study, it was an unusual study because of the expense. People had to have their insurance pay for the transplant itself, but after the study came out, the American Transplant Society said this should become standard of care.
So, it was successful?
McKown: It was so successful, which is really, really unusual. To have a study that comes in and just is so obviously beneficial that people say this is no longer experimental, this is what should be done.
Wow. How recent was that?
McKown: I think the article in New England Journal came out in like January of 2018.
So recent?
McKown: Maybe December 2017. (It was January 2018)
Was Chuck the first person to have that here, or in the state?
McKown: There was one person in the state who had a transplant at MCW as part of the study. We were actually in the study. We had three candidates, but their insurance refused to pay for them. Chuck is the first person since the study’s finished who’s gone through the process, which just goes to show that it’s not going to be very many people where this is going to be a good option for them.
Does the hospital or you benefit from the product or procedure?
McKown: Well, not really. I mean, it’s just medicine.
END OF INTERVIEW
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