Brain Kim, MD, a Dermatologist talks about chronic itch and the strong need for treatment.
Interview conducted by Ivanhoe Broadcast News in March 2018.
Could you tell me a little bit about chronic itching and what it is?
Dr. Kim: We’ve all experienced itch acutely meaning short periods of time like a mosquito bite. Chronic itch is when that itch becomes very persistent. We define it as itch that lasts greater than six weeks. And at that point it becomes a medical problem.
Six weeks is a lot longer than I would have anticipated. That’s a long time.
Dr. Kim: Yeah, it’s rather arbitrary but when itch lasts greater than six weeks we know that we’ve got a big problem and this is not something that’s just going to go away. You know this isn’t going to be poison ivy, this is not going to be something that’s just going to resolve. As surprising as that is most of my patients have been itching for months to years when they come in to see us.
When you say they’ve been itching, is it all over or is it usually localized?
Dr. Kim: Most of the patients we see have what we call generalized itch. It’s most parts of their body. It has a fairly consistent distribution but it really can affect almost the entire body from the scalp all the way down to the feet.
And how does this impact people?
Dr. Kim: It ruins their lives. In its severe forms is absolutely debilitating. You can imagine that if you don’t sleep because you’re scratching, it evokes anxiety. When you itch you start to feel anxious and then you get scared of itching more and then anxiety itself and the stress causes you to itch even more. And we know now there’s a lot of great research in sleep. If you don’t sleep well your health deteriorates, your mental health deteriorates so it just becomes a feed for a vicious cycle if you itch chronically.
This is a really serious issue?
Dr. Kim: It’s a serious issue in my view. I think that you know in medicine there’s a bias towards things that you know are life threatening and we can all appreciate cancers and major problems but a lot of my patients have cancer. A lot of my patients have very serious diseases that could affect their longevity. But they tell me you know what I’m not happy, I’m miserable what can you do. I’d do anything to fix this and many of them prioritize their itch over other things that we consider to be serious medical problems.
What causes it?
Dr. Kim: There are a number of known causes of itch. There are about ten percent of the population that suffers from a condition like eczema, itchy red scaly rash. You might know someone who has it. In that case we know what causes it. It doesn’t necessarily mean we know how to fix it that easily but we know what causes it. We know that if you have forms of cancer, if you have bad kidneys or liver you can also itch. There’s lots of ways that you can arrive at having chronic itch. It’s so understudied that a big portion of patients who have chronic itch we don’t even know what they have. We actually coined the term, we say chronic idiopathic peritis. Some people call it peritis with an unknown origin. By peritis I mean simply itch, it’s an unnecessarily fancy medical term. It means we don’t know what causes it. And if you look in medical text books that all medical students and residents study from, there are no chapters on chronic itch. There are currently no FDA approved treatments for chronic itch. It’s an area in which physicians are just essentially left to their own device which usually means that we really don’t do a lot for it. Of course we at the center for itch here are actively changing that and pushing the needle.
Before we get in to your research, what are some of the treatments that people do use now and then how effective are those?
Dr. Kim: The treatments that we use now are essentially medications that have already been developed for a lot of other things and we just kind of co-op it to try to treat itch. A good example of that is a medication called gabapentin. It’s used for diabetic nerve pain but we know that the same nerve fibers that cause pain can also involve itch. We use that medication for itch. Now is that what the drug was approved for, absolutely not. Have there been clinical trials? Absolutely not. But we as physicians have the freedom to operate, to use medications in new ways if we have to, to make patients feel better in the day to day. That’s an example of a medication. We use various topical steroids for itch, and topical steroids weren’t really designed to treat itch, they were designed to treat rashes but we do that. We take all sorts of creative approaches. How effective are they? Modest to moderately, depending on how clever we are. It’s very much dependent on the physician being able to recognize hey, you know this kind of itch I think we’ve had some good experience with this medication. But there’s no expert opinion, there’s no guidelines. This is a very kind of dark arena in terms of there’s not much light on what we can do.
These are all treatments that were developed for something else that you discovered might work?
Dr. Kim: Yeah, absolutely. That’s what we’ve taken and you contrast that to if you have high blood pressure there are guidelines in what to use first line, second, line third line; different populations. We are so far from that in itch.
Tell me how you discovered or concluded that maybe this drug for rheumatoid arthritis might work? Was that an antidotal finding somewhere along the way?
Dr. Kim: No, not antidotal at all. I want to be very clear about that. It came from basic research, basic science that’s funded by the federal government. It’s essential that’s the bedrock of innovation for clinical medicine. I think a lot of people think that research needs to be very practical, and it should be, but in basic mechanisms we have to look at cells, we have to look in mice and this is what led to it. It was not a hey, let’s just try this.
This patient got better on this and then doctors started talking more and more about it. This did start like you’re talking about.
Dr. Kim: It was a mixture and we call it bench to bedside meaning the lab bench to the bedside. But a lot of people say we’ve got to go from the bedside back to the bench. That’s what we do in our lab and in our center. What happened was we essentially had identified this molecule in the nerve that no one expected to actually be there. It was this completely unexpected finding. Even though JAK was thought to be involved in inflammation we thought maybe it’s involved in itch in the nerve. All itch has to go through your nerves back up to your brain. We thought we can block this and maybe we can treat itch regardless of the cause. That’s where it started and that observation then allowed us to then think what drug off the shelf right now can do this, and this drug was called tofasidren. The problem with that is that tofasidren is a very expensive drug for rheumatoid arthritis and a lot of research went in to developing that with never itch in mind. We had to be very persistent and creative about trying to get the medication for the patients. Early on before you know we actually had really flushed it all out we thought okay, let’s try this medication to see if we can help a couple of our patients who have just failed all medications. That’s where it started and those are the patients in our clinic. We’re grateful for them, for them to be willing to actually try new things but they all understand that. When I say that all medications are off label that means that nothing that we do is prescribed in any kind of guideline. And they understand that and that’s why they are here.
The way you describe it sounds like they would be willing to try anything.
Dr. Kim: They’re willing to try anything. In fact I would say that these patients have tried everything. Many of them have already tried medications that are off label from their dermatologist, their primary care physician. When they come to us what they’re really looking for is something new. They’re not looking for well let’s try this thing again that didn’t work last time That’s been our mission, how can we deliver the most cutting edge, the newest and really think deeply about how to solve the problem. Rather than say you know what, we looked on our shelf and we don’t see any medications that are going to work because if we’re going to think that way we can’t even open the clinic. You know we’d have to put up our close sign.
How many people are in your study and how did you design the study?
Dr. Kim: It was a very simple design. The study in our patients was not actually designed. What it was, was that we were simply giving medications off label to our patients. We noticed that they were improving quite dramatically. At that point we had already flushed out all of the basic science where we mapped out the pathway and really proved in a very convincing manner that this is exactly how everything is playing out. Of course that takes a lot of science. What we were able to do is now is collate all those patients, all the data we’ve gotten. And we get a lot of data in our clinic. And we were able to then insert that in to a bigger story really weaving together basic science all the way to a clinical outcome. If you were to hold that study alone up to a clinical trial it’s one of the earliest forms. I would say it’s what we call an early Phase II. But the beauty of it is that it is now inspiring big trials. Its informing and these class of drugs have actually came to the forefront of not just chronic itch but atopic dermatitis or eczema and you’re going to hear all about it from many, many different trials and companies now.
How long ago was this, when did you start looking at this drug and the pathway?
Dr. Kim: Not long ago. I came to Washington University here in St. Louis back in 2014 and we had made some clear observations in a Petri dish. And we thought wow, this could be something that’s very real. We investigated it further and we looked in mice and we start to get very confident. I proposed to a couple of patients, let’s try this arthritis drug. It’s relatively safe. We use medications that are less safe than that already in the clinic with very informed discussions about this. And they said, let’s try it and the results have been remarkable. The patients have been able to get their lives back, people are sleeping now that weren’t sleeping. As someone who sees chronic itch patients, they look completely different. After about four weeks of not having itch they come back in to the clinic and their mood is different, they look different, they look healthier. It all starts to come back.
What are the result percentages, what did you find?
Dr. Kim: Every patient that’s taken this medication has improved some with such remarkable results, everyone with significant results. We measure itch from zero to ten, ten being the worst imaginable itch and zero being nothing. Patients who come in with a ten they go down to a zero. That’s remarkable because even people with mild eczema have an itch score of two to three. There are actually people who are sometimes endorsing suicidal ideation. These are people who just can’t go on anymore with the kind of itch that they have.
Can you briefly explain how you guys think the drug works to stop the itch?
Dr. Kim: The drug was already discovered and it was used for rheumatoid arthritis because this molecule called JAK, Janus kinase and this molecule is very rationally designed to block that enzyme. The idea was that this drug blocks this enzyme that’s in all of these immune cells. It made since, rheumatoid arthritis is an inflammatory disease of the joints. If we block inflammatory cells we’ll improve rheumatoid arthritis. It is true it’s very effective for rheumatoid arthritis. The ah- ha moment for us in the Petri dish was that we realized that this enzyme was actually not just in immune cells but in the nervous system or in nerves. And that was not something we expected. Then we thought wow, what if we have a disease in which it’s not necessarily inflammatory like rheumatoid arthritis but neurologic like itch. If you said that for years ago to someone that you would use a JAK inhibitor like tofacitinib in neurologic disease people would have said, that’s kind of crazy, that doesn’t seem like sound logic. But that that basic science observation is what led us to say, ah-ha we can actually now approach this differently. Then we were able to say essentially take that drug at the same dose, give it to patients with chronic itch and now we’re blocking this in the nerve, so we think. It’s very hard to prove in patients but you know when we use mice and we use cells we can prove that definitively.
It’s already approved, it’s off label, you already mentioned that it was expensive. How likely is it that people really will be able to get this?
Dr. Kim: It’s been a mixed bag for me. We do science to help everyone across the country, everyone across the world. I can’t see all the patients with chronic itch. But we’ve have been able to help patients very dramatically who come and see us. But the mixed bag is that we have patients now calling us, e-mailing us saying how can we get this drug. And it’s very hard, it’s not FDA approved for chronic itch. In fact chronic itch is, right now, is not an indication that you can actually go for. That’s the first barrier. When a company wants to develop a drug for chronic itch, there isn’t a real clear pathway. A lot of this has to do with just the fact that this is so uncharted. This is uncharted for the regulatory agency, this is uncharted for clinicians. If it’s an uncertainty it’s very hard to charge ahead with confidence and clarity. That’s what we’re also trying to shape. Now I have high hope but if we can’t get regulatory pathway then the companies are not going to go for it, that’s one problem. But another problem, and I don’t want to just talk about the problems but another issue is that we know so little about chronic itch despite the fact that our clinic is getting flooded with patients from all over the country. We have a very small clinic here about half the country has come in terms of geography, patients from about half the country already to see us. One of the issues is that we don’t know much about it. When we say how many people in the US have heart attacks, I can spit out that data and I can look it up on line really quickly. When you say, how many patients have this form of chronic itch, not clear. How bad is chronic itch, how much is it affecting people’s lives. Is it up there with someone who’s had a stroke, maybe, maybe not we don’t really know. There’s so little information so often times the companies kind of say, well this is a big investment for us to develop a drug in this area. How many people suffer from this, how many people would actually want this drug? We don’t even have the academic machinery right now to answer those questions. There are a number of obstacles along the way. But we as researchers see that as an opportunity since we can now define all these problems and move forward and give people a pathway.
Right now somebody in another city across the country, say they have a doctor you’ve consulted before and he cannot prescribe or can he prescribe? Or will insurance not cover it?
Dr. Kim: Insurance won’t cover it. We can always prescribe it but the issue is that the insurance company says we’re not going to cover it. And out of pocket costs for that kind of medication is just prohibitive, that’s the problem.
It’s not affordable?
Dr. Kim: Out of pocket it’s over thirty thousand dollars a year. The mere fact that you have to ask me how bad is chronic itch is a problem. It means the public is not aware of this. No one is going to ask me how bad is pancreatic cancer. The fact that I have to say this over and over again, well now you can imagine with everything I have told you how many things we have to do in addition to not just advancing science. We also have to convey to people how big of a problem this is. Unfortunately for the patients who suffer with chronic itch, they’re suffering quite silently in that sense. I’m not pointing the finger at anybody but I think as a society we don’t have a lot of empathy for that until we suffer from it. I think that that’s something that needs to change. Because quality of life with chronic itch is terrible. Our charge as clinicians, as medical doctors is not just to extend life but to improve life. I fundamentally believe that.
What is the next step?
Dr. Kim: We’re already in the next step, we’re actually in the next two steps. We don’t believe that chronic itch is one disease; it’s not. It’s probably many disorders so we haven’t even tackled major issues you know. Something like forty percent, thirty percent of patients on dialysis have terrible itch. Even as a center we haven’t gone there yet. That’s something that needs to be tackled. And diabetes is associated with a much higher chronic itch. The next steps are to now expand it to other forms of itch. But with regard to what we’ve already done is to move forward and push for clinical trials. Define to people how big of a problem this is. Help really pave the way for a clear regulatory pathway where chronic itch is considered a disease and not a symptom of a disease. And just push this forward. A lot of it is we just keep publishing we keep doing the work and that eventually spreads the word. And what really happens is that once you hit a critical mass it’s kind of like the tipping point of patients who realize that we can do something about it. It’s really hard to say you know, we’re not going to do anything. So that’s our goal and that’s why we are appreciative to be able to talk with the media and such and really spread the word. Because every time we do this our inbox gets flooded. That’s not a study but that’s very telling. You can’t put a number to it, you can’t put anything to that. It’s a special feeling and that’s very, very inspiring.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Nancy Bodet
314-273-1376
Diane Duke Williams, PR
Sign up for a free weekly e-mail on Medical Breakthroughs called
First to Know by clicking here.
