Eczema Treatments: Present and Future — Dr. Peter Lio

Welcome to EGSMA Out Loud from the National EGSMA Association. I'm Danny Morsehead. My guest today is Dr. Peter Leo. Dr. Leo is here to talk about the many new treatments that have become available for people with EGSMA in the last few years. We'll talk about what those treatments are, including prescription treatments over the counter-treatments and natural and holistic treatments, and we'll also discuss how EGSMA patients should talk to their dermatologists about these new treatments. Dr. Leo, thanks so much for joining us. Can you start us off with an introduction? Hi, I'm Dr. Peter Leo. I'm a clinical assistant professor of dermatology and pediatrics at Northwestern University Fineberg School of Medicine, and I'm the founding director of the Chicago Integrative EGSMA Center. Great. We're so excited to have you here today. All right. So my first question for you is, how has EGSMA care evolved over the last decade or so? It has been absolutely incredible to see how quickly things have changed. And it turns out it's actually happening increasingly quickly. It's almost like an exponential rate of change that we're seeing. 20 years ago, when I first started practice, EGSMA was kind of a backwater of dermatology. There wasn't that much going on. We didn't have a lot of great ideas. Almost all of the medicines we used were off-label. It was really tough. And in fact, I tell the story that I'm grateful to Dr. Amy Paler, who was one of my mentors after I had graduated from residency and was in practice, because she kind of pushed me to focus on something. And she said, "You should focus on a topic dermatitis. I think there's going to be some big stuff happening there, and we need you." And it was just a great kind of a prescient choice to push me in there. And I will tell you that in the past decade, it has been unbelievable. With what I call the virtuous cycle of drug development, we get some new medicines. And that's great. Just in and of itself, it's great to have some new treatments after essentially decades of nothing happening. But what's fascinating is that those new treatments lead to new understandings. And better understanding of the disease. When we get that, then we get even newer and even better treatments. And this process keeps happening and it's accelerating. So now we're seeing more and more advanced treatments with all of these new options. And frankly, it is difficult to keep up. There's so many things happening. Great. Well, that's why we have you here today. And let's talk about some of those new treatments. What are the newest treatments that are available for people with XMA? So it's been incredible. Just the last couple of years, now we have a huge landscape. So let's start with our topicals first, because we know this is what essentially everyone's going to use topicals from the mildest to the most severe. And our topicals we've had for a very long time, of course, we have, and this we won't get into today. But there's also been huge advances in terms of just moisturizers and cleansers and sort of basic skincare, which is critical. And I don't want to undersell that, but I want to focus a little bit more on the prescription things today. And then maybe we can, at some other point, we can talk about some of the other over-the-counter treatments that are in some ways just as important as the prescriptions. But the prescription ones, we've always had our steroids, our topical steroids, they've been around since the 1950s, and they've been kind of stable. Then in the year 2000, we got our first non-steroidal agent. And that was the medicine, tachyrilitis. And then just a year later, in '01, we got pymacrylitis. And then nothing happened for 15 years, until 2016, when we got chrisaboral. The first phosphidesterase for inhibitor, so kind of another non-steroidal anti-inflammatory. And then in the last couple of years, we've had a flurry. So now, we actually have our first topical jack inhibitor, Janus kinase inhibitor, which is another powerful non-steroidal anti-inflammatory, that one's called ruxylidinib. We also have another PDE4 phosphidesterase for inhibitor, another gentle anti-inflammatory non-steroidal. And that one is called topical roflumelast cream. We have a whole new category that entered very recently, and that's an aryl hydrocarbon receptor modulator, technically it's an agonist, meaning it actually binds to that receptor and activates it, and that's the medicine to pin it off. And then we just got yet another jack inhibitor. And this one's technically indicated for chronic hand eczema, so specifically for hands. And that one is called delgocidinib. So we have all of these incredible new treatments that we can pick from that are non-steroidal and really powerful, and all have passed muster in terms of safety and efficacy. We moved to the systemic agents, again, back in the day, we had essentially nothing. Our first big breakthrough for the first real FDA-approved medicine for atopic dermatitis as a systemic agent was dupliamab. And dupliamab came out in 2017, it was a very big deal because we just had nothing like that before. And of course, that's a biologic, it's an injectable agent, and it blocks IL-4 and IL-13 to really important inflammatory triggers for allergic diseases. And it turns out we know this in part, as I was saying, that virtuous cycle, because now we know that dupliamab can be used for many things. It has an indication for atopic dermatitis, but also for paragonal gelaris, these itchy bumps, and also for asthma and eosinophilicusophageitis, and all these different conditions. So it's really amazing to see how it can play a role for many different disease states. Then we got a cousin of dupliamab called tralocinumab. And that one is nice, that one binds to IL-13 directly, it's kind of similar in many ways to dupliamab. And then we even have another one that's in kind of the same sort of family, and that one's called leberchismab, that also binds to the IL-13 cytokine. And it's pretty powerful. So all three of those kind of work similarly, they have maybe their own little strengths and weaknesses, they're all kind of unique, but they're similar. And then we have our two oral agents, and those are oral jack inhibitors. So the Janus kinase inhibitors, powerful anti-inflammatory treatments, and that's eupatocinative and abracinative. So this is really quite a palette that we get to choose from now. In just a few short years ago, we essentially had none of it. We have a new biologic that just got entered, that's totally different. And that one blocks the IL-31 receptor, which is sometimes called the master itch receptor. And that one is called nemolizumab, and it's really exciting because it really targets itch primarily, but it also seems to help with inflammation and also the skin barrier damage. And what's nice as well, it's really new to us in the United States. It's been out in Japan for a few years, so we actually have a little bit more knowledge about it. And I'm really excited about this new entry into our armamentarium. Awesome. So all of these, except for the last one, are available now? Even the last one, all the ones I mentioned are available now. And then you can't even imagine the pipeline coming. There's so many medicines in the pipeline, like I can't keep track of them all. More than, honestly, more than a dozen different ones that I'm aware of, and from what I've heard there are even over a hundred that companies are looking at. Yeah, that's so incredible. What an exciting time for people who are seeking treatments. All right. What are important questions Exima patients should ask their dermatologist when discussing trying a new treatment? I think the key thing here is that we really want it to be a shared decision. We want the patient and the patient's family when that's appropriate to be part of the discussion. Because at the end of the day, it's not just that we want someone to get better or feel better. It's that we want them to feel good about it. We want them to feel comfortable with what's happening. We want them to be able to keep it up. All of those pieces are part of the puzzle. So I often frame it in terms of the word a star, right? In Spanish, a star means to be ESTAR. When I think about these different attributes of medicines, E is for efficacy. How effective is the treatment and, of course, treatments vary in their efficacy and, of course, it varies from individual to individual. There's no doubt that some medicines that work really well for some patients don't do much at all for others, but it's still a question we can ask. This one generally considered more effective or less effective and, of course, we can even break that down. How quickly is it going to work? How deep is that response going to be? How durable? How long can I expect this to keep working? All those are key pieces, but E is for efficacy. S is for safety. Safety is really important, too, because if I told you I have something that's going to make you feel great, but there's all sorts of serious risks, well, then you have to make the calculation. That's very different than something that I might say. It's going to help a little, but it essentially has no risks, or they're very tiny risks. And we have the whole range in dermatology, and, of course, even within a topic dermatitis, so that's safety we have to discuss in detail. Then we have tolerability. This is a little bit different than safety. Your vulnerability means, you know, how does it feel going on the skin? Is it stinging? Is it burning? That's not dangerous, but it's really unpleasant. Or is it greasy and uncomfortable? Or is the shot, I mean, if I told you you had something you had to do a shot every day, that would be really tough, right? It's like, gosh, this is going to be really intolerable to do this all the time. So that's part of the discussion. And different treatments have different strengths and weaknesses there. The A is for accessibility. Can you get it? All of the new medicines, well, actually most of the new medicines are really expensive. So without a good insurance or the company supporting it, I mean, nobody can get it unless you happen to be Jeff Bezos or something, in which case, you probably aren't listening to this podcast because you're on your yacht somewhere, right? But most of us can't afford to spend $40,000 a year on a medicine in perpetuity. So we really need that kind of access. And that's important. And I'm happy to say, for the most part, all the medicines I discussed today are fairly accessible, but not without some issues. And sometimes we have to really fight for them and write letters and do all these things. And then the R is the kind of the newest, most interesting one to me. And this is the idea of something being remittive, something that could potentially put the eczema in a remission state, a quiet state where patients might say, hey, you know what, I'm doing great. Would it be okay if I took a break or spaced it out? And it turns out that some of the medicines we mentioned, in fact, trailociniumab, lebrachizumab, and nemolizumab all have built-in, built into their prescribing information, the ability to cut the dosing down by half, which is crazy. So for example, with nemolizumab, one of the newer ones, it starts out as a monthly dosing for a topic dermatitis, but when people are doing well, they could go to every other month. With lebrachizumab, another one of the newer ones, it starts out at every two weeks for adults and for kids down to age 12 years. But then when they're doing better, after 16 weeks, they could potentially go to every four weeks. They go to monthly dosing. So half as many doses. So that's great. I would argue that is kind of a remission. And then some of my patients, and I even wrote a paper about it a few years ago, are actually able to come off of something like depiliumab or one of these medicines completely and be much better. Now, are they cured? Unfortunately, no. I wouldn't say they're cured, but they're much, much better, and they're in a much more stable state, and they're able to do what they couldn't do before on gentler approaches. Maybe it's just their topicals, or maybe they're just doing light therapy now, or maybe they just can be careful with certain triggers and things, and they can use good moisturizers to stay clear. It's really exciting to see that. Excellent. Thank you for the mnemonic and for all the information. All right. What alternative and holistic treatments are you commonly recommending to patients these days? So you know that's one of my areas of interest, and I'm always learning new things, always reading new things, and experiencing them with my patients and families, and often learning from patients about what works and what doesn't. So I'll give you a couple of my favorites. One of the big ones has been black tea compresses in the past few years. It's been so powerful. There was this wonderful study out of Germany showing that people with really bad face and neck eczema in particular on their face. If they literally, you just take some plain old black tea, and it should just be black tea, not anything with flavoring, or with bergamot, or anything, just plain old black tea, brew up a cup, and then you can drink that cup or pitch it, and then using the same tea bag, do a second steeping. The second cup writes a little milder, a little weaker. Then you take that, and you put it in the fridge, so it's nice and cool. Then throughout the day, you take a little cloth, and you don't get in there a soft wash cloth, and you just do it as a cool compress on your face, neck, or really anywhere. And I have patients do that multiple times throughout the day. It's cooling. It's soothing. It's kind of hydrating. You should put moisturizer on right after, but it's really powerful. So that's something that I've used a fair amount with really could effect. It's kind of changed my practice. The other one I'll mention today is something that I came across way back almost 15 years ago now, and it was a really interesting paper about how topical vitamin B12 can actually sue the eczema. And I thought, boy, this is a really well done paper. It seemed really, they had a control group with a placebo, like I'm like, this is really well done. And then a second paper kind of reproduced it. They showed that this actually bore out when they did it again in kids. So we really have some nice evidence. But I couldn't find a product that had the same kind of concentration of vitamin B12. So I worked with a small kind of office in the Chicago area. Technically, he was an aroma therapist. He kind of focused on essential oils and a perfumist. He had a degree in being a perfumist, working with natural essences. But he was able to help us put together in small batches topical vitamin B12 cream. And one of the first patients I gave that to really liked it. I said, so do you like your B12 cream and she looked at me and looked up at her mom and said, what is that? And the mom said, you know, your pink magic. She had called it pink magic because it's kind of this beautiful, shocking pink color when you mix it. There's no, there's no dye in there. It's just it turns out that cobalamin, the vitamin B12, when you mix it into a moisturizer base, it turns kind of this beautiful bright pink. It's like a crimson red naturally. And it was so cute. So we've always called it pink magic since then. So those are two things that I think can help. One of the things my patients ask me about a lot is what about the role of diet? And we change it with diet. And the answer is yes, but it ends up being a lot more complex than I wish it were. I wish I could just say, yep, cut gluten and dairy and you'll be cured. It's just that. But it is so much more complicated than that for most people. And in fact, most of my patients have tried pretty serious diet changes. And if come, come away kind of frustrated, like, you know, maybe it got a bit better, but it didn't really get me all the way. It didn't seem to be the whole thing. And then of course, we know that really strict dietary changes are very hard on you and it's particularly stressful for kids. So of course, we can go on for quite some time. But those are a couple of my little take homes and certainly always happy to talk more about that. Great. Yeah. That's a whole separate podcast right there, the diet. It's like about new treatments that haven't come out yet. So what are we looking ahead to? Any new research or emerging treatments that you're excited about? Yes. There are a ton of them. And again, I literally, and I say this truthfully, I'm overwhelmed. Like I cannot keep up. I'll be at a conference and people will say, hey, have you heard about this new? And I'm like, nope, haven't heard about that one yet. There's just so many things. But in general, a couple of things I'm super excited about. One are things that are going to help the microbiome because this is an area that we understand is super important in eczema that there is an imbalance, both in the gut, but also on the skin. And there are some companies working on some topical and oral probiotics and probiotic mixtures, ways to kind of rebalance it. And we really think that it is possible, at least for some patients. And we're going to find out in the next couple of years, is these studies come to fruition. But we really think that the right balance for the right person could actually do a ton of the heavy lifting and fixing that microbiome might actually be a way to healing and a deep kind of healing that doesn't require suppressing the immune system or doing things that are going to screw up the skin barrier, all these kinds of things. So microbiome is one and there are several companies working in this space, topical ones as well, which I think are fascinating. Another area that's really exciting to me are there are some ways to target staff bacteria that are safer and better because it turns out part of the issue when the microbiome is imbalanced. One of the bad things that happens is staff-oriented bacteria grows like crazy, it releases a whole bunch of nasty toxins and these toxins like alpha toxin, delta toxin, V8 protease. All these things can drive inflammation, they drive itch, they can do all this bad stuff to the skin barrier. So if we could knock out staff, that would be great. The problem is if you use an antibiotic or a broad spectrum kind of thing, you can really damage the whole microbiome. It's very, very tough on the microbiome because you hit a lot of the good guys. So there are some companies working on some newer treatments, some of which are actually kind of found in nature that can zap staff or is very selectively. And I think if this works, it will be incredible, it'll be an incredible way to do it in a very safe way that's not damaging to the whole microbiome. And we have tons of innovation happening in terms of the understanding of the immune system. And there's actually several medicines built around this pathway called ox-40. Ox-40 has an effect on some of the T cells, those cells that are playing a role in this whole inflammation pathway and it's possible, or at least it's theoretical, that if you can block this pathway and sort of push that down, that you might get a remission. The big idea with the ox-40 pathway is not only will it help in the short term, which would be great, but that basically when you stop it, hopefully will kind of reset the immune system in some way. And so people might be able to come off the medicine, which is super exciting. And then sort of another last one, because again, there's so many, it's hard to keep them all in mind. But one that's also interesting is an area where they're actually mixing multiple of the targets that we already know about. So I mentioned like one of the the biologic agents blocks IL-13 and other one blocks IL-31. While some companies are working on combinations together, pre-packaged combos. So they're calling them bi-specific antibodies. And I think there's some real potential there. We could sort of hit just a couple of the key targets very, very safely and not have a lot of collateral issues happen. So that's another really exciting area. And I just can't wait to see in the next couple of years as these things come out and as we get more and more studies on them. Now, some of them I'm sure will get thrown out. Sometimes we think we have something and say, "That's not safe enough. It doesn't pass muster or it's not effective enough. It's not going to get there." But I have a good feeling about some of these at least. And I think we're going to see some big, big new entries that are going to change the decision-making matrix for us and our patients. Excellent. So exciting. So much on the horizon. All right. Last question for you. How close are we to getting an actual cure for eczema? I mean, I'd like to think that we continue to move in that direction. Every time we get new treatments, every time we get that virtuous cycle of drug development and understanding, I really think we're getting closer. I don't think we fully understand the disease yet, though. We still have a lot of confusing aspects, probably because it's not just one disease. We really think that there are probably multiple different versions of it and people can start in different places. But they all kind of look similar, even though arguably people can look pretty different with their eczema. We really think this is probably not one simple answer. But I do think, for example, if the microbiome is a big problem and if we could find a way to stabilize the microbiome and strengthen it, it is possible that we will come up with something like a cure for some of these people. I think now part of the problem is it's like, why did the microbiome get wonky in the first place? And this is the problem with this disease and diseases like it. It's probably, again, not just one simple gene mutation or one simple problem. It probably can be a lot of different susceptibilities and we live in this pretty intense world. We have a world where we're eating foods that have emulsifiers and things that can damage our gut barrier. We have clothing that we wash frequently with residual detergent that can damage our skin barrier. We're constantly bathed in different pollutants in our air, especially people that live in urban areas or industrialized areas. There's fuel, you know, car exhaust, fuel exhaust, there's industrial stuff in the air. There's California wildfire smoke, which was remarkable in Canadian wildfire smoke that we're often being exposed to and it turns out that wildfire smoke can actually trigger barrier damage and damage is the microbiome as well, which can start this whole process. So I don't know if we're going to actually be able to cure it for everybody, but I'd like to think that if we can figure out, okay, in this particular patient, they have a little bit of barrier susceptibility. So if we can just boost up their skin barrier, we could potentially protect them and prevent it. And the last thing I'll say about that is a really exciting study just got published a few weeks ago. The lead author was Dr. Eric Simpson. He's a friend of the National Examin Association. He's an eczema expert and champion who's out in Portland and they completed a large studies showing that babies who use moisturizer from basically just the second month of life. So once they're about nine weeks old, they start putting moisturizer on them. When they compared this to a group that wasn't doing that, they were able to significantly reduce new development of a topic dermatitis. So cure would be the, would be great. I would argue that prevention would be even better, right? Preventions even better than a cure. We don't have to deal with it in the first place those patients are spared and could you imagine if it's just using a moisturizer. That would be amazing. Now, I wish I could say it worked for everybody. It didn't, but it helped a substantial number of patients more than the control group that were able to not develop signs or symptoms of eczema and that's pretty exciting to me. Wow. That's super exciting. Okay. One more question for you. What is something that might be overlooked that you're most excited about in the eczema space right now? There are so many things as you've heard and I honestly legitimately am excited about essentially all of them, but for me, the area that I'm most drawn to right now is thinking about the role of over-the-counter treatments. I think that they are sort of this sleeping giant, so to speak, that are often ignored or at least don't get the respect they deserve. So many patients are going to look to that area first. They're going to go to the drug store. They're going to look in the aisle. They're going to see advertising online and they are going to be looking for products that are not necessarily prescription. And of course, we understand that with increasing concerns around some of the prescription and powerful medicines, I have more and more patients saying, please, can we try to do other things than prescription therapies? We want more natural, more gentle ways. So I have to say that one area where we don't see all the same kind of innovation discussed as much is in the over-the-counter world. But it's happening. It's happening incredibly in some of the companies are spending fortunes working on research and development in, I mean, it sounds almost kind of silly, but in the cleansing space. Like there are some new cleansers that are absolutely magical. They're gentle, but they still do a good job. They're restoring of the skin. They're non-irritating, non-stripping. And you can get them for like $9 at the drug store. So that's important. And I feel like I want to convey this to my colleagues. I want to convey this to patients that, yes, the powerful prescriptions are key for the people who are suffering. And I am so grateful for them. But for the vast majority of patients, they're still going to have to use and want to use some of these other gentler products. And if we find good products out there, great moisturizers and the huge leaps we've taken with moisturization technology, understanding them, just in my career, it's been incredible. That could be a huge deal maker for so many patients that maybe we're going to be between doing okay with topicals alone and needing to go on a systemic agent. Finding the right suite of just gentle skincare products, I think, can make or break it for so many people. And I just love to see all these companies putting in time and energy and taking it very seriously. And that's to me is probably the single most exciting thing right now. Great. Well, thank you so much for joining us for this chat. Thank you for having me. We'd love to have you back in the future. It's always a pleasure. And on behalf of everybody in the Eczema community, thank you for coming on this podcast and doing the many things you do for everyone who has Eczema. Totally. Thanks, Danny. Talk to you soon. Thanks for listening to this episode of Eczema Out Loud. You can visit the National Eczema Association at www.nationalexma.org. If you have feedback on this episode or you'd like to send in a suggestion for a future episode, you can email us at [email protected]. We hope you'll join us next time.