Derm-it Trotter! Don't Swear About Skincare.
Feeling frustrated or overwhelmed with everything skin? Does the skinformation overload make you want to swear about skincare? Join Dr. Shannon C. Trotter, board certified dermatologist, as she talks with fellow dermatologists and colleagues in skincare to help separate fact from fiction and simplify the world of skin. After listening, you won’t swear about skincare anymore!
Derm-it Trotter! Don't Swear About Skincare.
JAK’d Up: Smart Science, Real Talk
Dr. Raj Chovatiya breaks down the science and myths behind JAK inhibitors—powerful meds transforming dermatology. While black box warnings sound scary, he explains they’re based on higher-risk arthritis patients, not those with skin conditions.
Unlike biologics, JAK inhibitors work inside cells to block multiple inflammatory pathways, delivering fast results—itch relief in days, visible skin improvement in weeks.
Dr. Chovatiya also shares what to really know about side effects, monitoring, and the shingles vaccine. With growing uses beyond eczema, JAKs are changing the game.
Listen in for a clear, honest look at these innovative treatments.
Welcome to the Dermatrotter Don't Swear About Skincare podcast. We've got an exciting episode here for you today. We've got Dr Raj Chovatiya. He's actually a clinical associate professor at Rosalind Franklin University, chicago Medical School, and founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, illinois, and I'm so excited to have him on here today. So welcome to the podcast, raj.
Speaker 2:Thank you so much for having me, Shannon. It's a real pleasure to finally make it to your VIP guest list.
Speaker 1:Well, you've made it. You're up at the top as a VIP, so it was worth the wait to get you out here and on the podcast. And I really wanted to bring you on because in the dermatology space and patients are aware of that and some of them out there might even be on one of these drugs you know this kind of you know, elusive class of the JAK inhibitors that you know a lot of noise has been made about, obviously with dermatologists and other specialists, but then a lot of I think you know fear amongst patients about what do these drugs really mean and are they right for me? And what I wanted to do is bring on today to really just bring some clarity to what these drugs are and how they might be able to help patients and maybe alleviate some of those concerns people have. So I'm just going to get started with asking you just kind of outright you know, what exactly is a JAK inhibitor and how does it work?
Speaker 2:Great question, and you know it seems somewhat basic when we're talking about this from healthcare provider to healthcare provider, but you'd be surprised how many folks who haven't had a chance to really use JAK inhibitors or participate in studies or think about them actually find this to be a little foreign as well. So I like to describe JAK inhibitors as really a small molecule that works on the inside of cells that are overactive in your immune system. Now there's other cells in which they're relevant, but at least for the purposes of our disease treatment, really, we like to think about this drug class working across multiple different types of immune cells. Now, the reason why that's important is that, you know, some people might be more familiar with our injectable biologic therapies. We've had them for longer. They're big antibodies that you go inject directly into the bloodstream and or the subcutaneous area. They bind to very specific signals that hang around on the outside of our cells.
Speaker 2:But JAK inhibitors do a little something different.
Speaker 2:Rather than very specifically targeting one signal or the other, they actually work at a lower point in that pathway, across multiple cells for multiple signals, and so the way the human body is designed.
Speaker 2:It's a very cool feature of evolution, is there's really only a small handful of ways that signals are transmitted through cells. You can almost think of it as a relay race. You got someone handing something off to someone, someone handing something off to someone else. Eventually this goes into the powerhouse of the cell, the nucleus, where there's transcription, translation and proteins and stuff made. So transcription factors are activated as a result of the Janus kinase family in a lot of cells or the JAK family. Jak inhibitors essentially just stop this relay race at a different point for a lot of different signals and stop inflammation in several different ways, and that's one of the reasons why they're a very exciting class of drug that can work across so many different kinds of diseases of drug that can work across so many different kinds of diseases and now that you're talking about those kind of diseases or you know states that we kind of really look to do treatment where particular in the skin.
Speaker 1:you know, are we looking at obviously now where we use JAK inhibitors and where do you think we're going in the future?
Speaker 2:So some of the oldest studies for JAK inhibitors were actually psoriasis and, as it turned out, JAK inhibitors were just okay for psoriasis. It turns out that there's some other signals that work through non-Janus kinase mediated pathways that are important here, and so they didn't really go that far forward. But what ended up happening is, in a lot of different case reports, case series and just uses of other Janus kinases in the real world, people found out hey, some of my patients with eczema seem to be doing better, Some of my patients with vitiligo seem to be doing better, Some of my patients with alopecia areata seem to be doing better. And this is kind of how the whole Jack inhibitor revolution started and thus began a series of phase two and phase three clinical trials for a whole bunch of new small molecules in oral and topical format to look at a variety of different dermatologic diseases. So in today's day and age we have oral gynase kinase inhibitors that are approved for the treatment of atopic dermatitis as well as alopecia areata, and we have topical gynase kinase inhibitors that are approved for the treatment of vitiligo and atopic dermatitis.
Speaker 2:Now this list is growing pretty rapidly. We're going to soon have oral treatments that are approved for hydradenitis suppurativa and vitiligo. We're going to see topicals potentially moving into this HS realm and perhaps some even less common dermatologic diseases like our lycanoid diseases may see an approval there too. But the next man up is going to be a disease called chronic hand eczema, where hopefully we'll have a new cream that's also a Janus kinase inhibitor later this year. So whether or not it's a class of drug that you feel very equipped to talk about, you're going to have to because they're touching so many disease states that we see in our everyday clinic.
Speaker 1:So if a patient is kind of walking through the clinic and you take a look at them and say, okay, yeah, you've got atopic dermatitis, I think a JAK inhibitor would be appropriate for you, how would you explain that it's going to help, maybe in terms of their actual rash or their itch or quality of life? What are the expectations that you really talk to them about, about improvement, that they might see?
Speaker 2:A question that comes up all the time, because, at the end of the day, in every atopic dermatitis visit, I try to make sure patients understand that they have multiple treatment options, and I have no idea, really, when they walk in through the door, which one is going to be the right one for them, because a lot of it is dependent upon how they feel, based on what you say. So you have so much power as a healthcare provider to really provide information that allows people to make the right choice. And so when we're talking about Janus kindness inhibitors, let's refer to oral therapies for moderate to severe disease for a moment. These are going to be once daily pills that are available in a couple of different doses low doses and high doses that allow us to very flexibly treat the signs and symptoms of disease and to just prepare somebody for what might happen.
Speaker 2:One of the coolest things about oral Janus kindness inhibitors is how fast they work and how potent they are.
Speaker 2:So, when it comes to thinking about itch as the primary symptom of atopic dermatitis, most of our Janus kindness inhibitors have data showing that it's really we're talking about days that you're starting to see somebody actually having a clinically meaningful improvement in itch, and then, when we start thinking about significant milestones for improvement of the actual inflammation that you see in the skin lesions, this is really only on the order of a few weeks. So, frankly, you may have a lot of information in the course of, let's say, a month, compared to another type of therapy that works a little slower, a little differently, where it may take you several months to figure out what's going on. Now, the other cool part is that, even if we don't get to where we want to, we have the ability to go to an even higher dose as well. And that's the other part I like to remind folks as well is that, even though I say all these good things, it's one of those. Wait, there's more. We may be able to even escalate you to another dose too.
Speaker 1:So with knowing that and the flexibility in dosing and the improvement that you know might actually be seen for these patients. You know, I like to talk a little bit of like the elephant in the room, if you will. You know, for the JAK inhibitors what everyone kind of fears, not only, I think, some of the healthcare providers listening out there, but our patients that are aware of this. You know, box warning. That does appear on the Jack inhibitor class. Do you mind explaining a little bit about even you know what a box warning is, other medicines that might have a common things? You know, like an ibuprofen, and what does it really, you know, mean Like why do they actually have one, just to put it in context for a patient?
Speaker 2:So this is a. This is a good piece of bedtime reading here, so I'll try to give maybe a medium version of this story, but what I want to tell anybody listening out there is this is actually relevant, because some shortened version of this is a part of every conversation I have with my patients, because it's really the only way to provide appropriate context for what looks crazy and scary on labels but may not actually be as worrisome for many of the people that are walking through your office as you might think.
Speaker 2:So when it came to Janus kinase inhibitors, this is a large class of medications and sort of the granddaddy of this class was a medication called tofacitinib, a small molecule that was a pan-JAK inhibitor, meaning that had activity across all four JAK proteins, and it was originally approved for rheumatoid arthritis. And in those studies let's say a couple of decades ago or a decade and a half ago what they found was that huh patients were doing better. But there seemed to be these rare events and not the kind of rare events we totally love People that potentially may have some major adverse cardiovascular issues, potentially some blood clots, maybe some malignancies, maybe even some death related to those as well, but these are very rare signals. In any clinical trial no matter whether you're thinking about people at high risk or low risk it's hard to spot some of these particular events. And so there was a mandated study that was done to look at people that were compared to standard of care therapy versus this medication, tofacitinib, that were followed for several years and what they wanted to do was understand, from a safety standpoint, is this really a risk we should worry about or not? And for this type of study, the deck was really stacked, because, at the end of the day, if you wanted to catch these kinds of events, if you had a regular population, you'd this study for like 100 years, right, and like no one's sticking around for 100 years, let me tell you that right now. And so they took people that were all over the age of 50, that had a variety of cardiovascular risk factors, that were all on immunosuppressive therapy with methotrexate.
Speaker 2:About half of them were on some type of corticosteroid therapy as well, and so already this isn't sounding like your average atopic dermatitis population, but all these parameters were true, and they all had rheumatoid arthritis a very different disease state and these patients were treated with either tofacitinib or an injectable medication called the TNF-alpha inhibitor, something that we used to use a lot of in dermatology for psoriasis, but is used a lot as first-line therapy for people with rheumatoid arthritis. These people were then followed over the course of several years. Some people managed to stay on therapy for a few consecutive years, and what they were really tracking was a variety of non-inferiority margins for some of those adverse events that I listed and, as it turned out, there seemed to be a relatively higher, increased incidence of major adverse cardiovascular events, infections, malignancies, venothrombolic events and even death. Now the funny thing is that, across all these groups, it's possible that the overall rate of these events is still a little lower than patients with rheumatoid arthritis, just because they already are a sicker patient group, especially older patients. But compared to the TNF-alpha inhibitors, these events were a little higher, and so this led to the FDA making a boxed warning on all JAK inhibitors oral, topical, any way, shape or form that. Hey look, because of this medication that is related to the rest of this class. Here's things that you really need to be worried about, potentially in people who might have certain risk factors, or tobacco users former or current tobacco users in the case of smoking and so this wording repetitively appears on both our topical Janus kinase inhibitors like ruxolitinib, as well as our oral Janus kinase inhibitors for atopic dermatitis, upatacitinib and abracitinib.
Speaker 2:Now, what does this mean to me as somebody who is in dermatology, talking to an atopic dermatitis patient? Well, it's something that I have to talk about and address, but what's interesting is if you follow most of these adverse events in patients with atopic dermatitis. It's a very, very different story and we can touch on that if you'd like, but I think what I want the listening audience to think about is probably everything I just spent a few minutes talking about. You can boil that down into a few sentences to give your patients some context. Hey, you look at the paper that comes with this drug. You might see some big, scary sounding words. They're going to be in big, bold letters in a big black box. What exactly does that mean?
Speaker 2:Well, a medication that is essentially related to this medication the first one of this particular family was studied in patients with a different disease, patients who are older, sicker on other medications, with a lot of different risk factors, and they found that there was increased rates of some of these scary sounding things infections, malignancy, thromboembolic events, and so that's put on there just to give everybody reminder that that was seen.
Speaker 2:Now, what does this mean for you? The eczema, homobolic events, and so that's put on there just to give everybody a reminder that that was seen. Now, what does this mean for you, the eczema patient that's sitting in front of me? These were all events that were seen extremely uncommonly in patients that were treated with atopic dermatitis, whether in monotherapy or in combination with topical steroids, and in some follow-up studies that we've looked at. When you take a look at the whole population of eczema patients, these are probably somewhere in the ballpark of where you might expect to see some of these rates. So what does that mean for me? Well, we'll talk about your health every time that I see you, and I want to know about what's going on with you, but my concern is not that high for X, y and Z reason, and that's about it. That's how you can actually very succinctly present this to a patient without causing any unnecessary alarm.
Speaker 1:I love that because you know, unfortunately, with box warnings, you know they're important, the FDA feels like it's important for us to know. But you really put it in context, you know for the patient, just to get that you know more realistic understanding. And I think, too, you're reassuring them that yes, this is something that's highlighted, but again, you're not as concerned because you know different population and looking at them and how they're being treated. So that gives people, I think, a nice balance and may help them feel a bit more comfortable about starting a medication like a JAK inhibitor that carries that box warning. You know, if you think about somebody who you know you've talked about going on a JAK, you've sort of convinced them. You've had that spiel right now that were there, okay, feeling good about this. And you know, with regards to some of those safety, you know concerns around JAKs. What do you talk to them about? Sort of the lab work piece. You know why are you doing it, what type of labs are you planning to order and how often do you tend to follow them?
Speaker 2:Sure. So labs are actually pretty easy with JAK inhibitors because there's a few things you're going to get in the beginning, maybe a little bit of stuff after being on therapy for a few months, and then at that point it's really totally up to you. So at baseline, for any patient that's going to be on a systemic oral JAK inhibitor, you're going to want to do a little bit of infectious workup, very similar to what you might be used to with some of our psoriasis therapies. This would be looking at TB status, oftentimes through a blood interferon release assay, hepatitis B, hepatitis C status. At that point there's some subtle differences between all the drugs. So what you might see on the label for abracitinib, baricitinib, upatacitinib, or even what you might see for duraxolitinib, whatever get there, whatnot they all have slightly different nuances and so you might have a different lipid monitoring. So some of them are about one month from starting and baseline. Some of them are, look at, three months. You might have slight differences in terms of whether you're looking at a CBC or a blood test. You might have a different nuance in terms of whether you're particularly taking a liver function test. Some people like to throw in metabolic panels in there too.
Speaker 2:That part I won't bore everybody with the details. Read the label because I think it can be giving you good guidance. But here's the thing Don't over-order labs. If you order your labs at baseline and at an appropriate follow-up time, every one of these labels says at that point it's as clinically directed, and I take the FDA.
Speaker 2:If we're going to complain about boxed warnings, I'll take them for their word. If they say it's as clinically directed, then I'm definitely incorporating that to my practice and as someone who's sort of been with a lot of these drugs in various phases of development or participated in many of these studies, I can say that for lab aberrations not super common Typically if they're going to happen it's usually within the first month or two and in most of these studies patients were resolving or resolved for many lab changes. With JAK inhibitors in particular, it's kind of a I won't make a blanket statement but for most of the oral jack inhibitors it was really around probably the six to eight week mark that maybe you might see some of these things. But that's the reason why I try to push some of my lab checks to be a little after that, just because then you're not going to catch something that you don't want to have to follow up on. Anyway, I'm sure you're a lot like me where you hate to have to deal with labs.
Speaker 1:And patients hate that too. As you know, it's a lot of undue anxiety. You know, when you find something and you try to explain to them well, but based on the evidence, like it can be transient these things tend to bounce back. This is just where we initially saw it, and so maybe it's better to check a little further out, just so we avoid that predicament for the patient. So, in addition to labs, though, if you have somebody coming, okay, I get the box warning, okay, I get it. I understand that. That's you know in the context. I'm okay, I get the lab piece. Okay, what about the side effects? What are you going to tell them, raj, about side effects that they should just be on the lookout for and make you aware of if they're experiencing any of?
Speaker 2:them. So with our JAK inhibitors. Really there's only a few things that truly seem to be drug related from the am I slightly concerned route, and the rest of them are all just kind of adverse events that you think about with clinical trials. So I'd say that in terms of like the big and bad and I use that in quotations I mentioned herpetic infections with my patients because that's probably real to various degrees, based on the JAK inhibitor and based on the dose. If you have a history of herpes simplex or genital herpes, I like to remind them let's make sure that you have your valacyclovir on hand in case you do have a breakout, because a small percentage of people might have a breakout with this particular therapy. Shingles is another one. Herpes zoster, right, that is seen at low rates does seem to be dose dependent and it may depend on the drug itself, but that's also a possibility. So I like to talk to my patients if you're age appropriate getting the shingles vaccine, otherwise just keeping a lookout for this or if it's something they want to even consider. I will not start therapy, but it's at least something I like to put in the back of their mind. The last one is infections. Now, those count as infections. But typically when I say infections, upper respiratory tract or sort of even lower respiratory tract infections were things that were seen in these studies. It's tougher because we see these across a lot of studies as well, but it's at least something I mentioned. After those three, I don't spend as much time on those boxed warning elements as one might think. I spend more time on what's specific to that drug.
Speaker 2:So let's take upatacitinib, for example, the one at the top of that list acne. We see that in various degrees with all of our JAK inhibitors. But this is probably the signature event of upatacitinib. Seen it several times in the real world usually ends up resolving without much intervention or maybe the mild use of washes or topicals. It's not usually a major treatment stopper for my patients. In the case of abracitinib, it's sort of this nausea, headache kind of picture with a lower degree of acne. Is this usually something that's a major stopper for my patients? Not really. They take it with food and water and usually it ends up not being a lasting side effect. The others have similar signature side effects but almost all of them have adverse event lists that have the regular old stuff that you'd expect from any other drug.
Speaker 1:When you mentioned the shingles vaccines, I do think for a lot of people that that scares them or they know somebody obviously who's had it and how miserable they potentially were with actually having shingles. If you recommend getting the vaccine, do you recommend starting, obviously, that initial vaccination prior to getting on drug and then are you comfortable with them doing it while on drug or do you have them take a break for that second shot?
Speaker 2:Yeah, we know how difficult it is to get people in the office in the first place, and once they're there, I really want to make it worth their time and effort, because they sought me out to be able to help them. So I'll get started on therapy If I have samples to give them that day. We'll get samples going on that day If they decide that they want to pursue a shingles vaccine. The great news is that we no longer have to think about the live vaccine anymore. Pretty much everybody gets the non-live version. Most of our drugs have data for non-live vaccination. In the case of upatacitinib, it's not specifically from the atopic dermatitis program, but it's from the rheumatologic disease program, and there they looked at people with vaccine responses. There wasn't much of a difference, and so for non-live vaccines, I don't tend to make a big deal about people taking gigantic breaks For live vaccinations. That's a separate story and there's less of those. So I guess measles is back in our discussion in the lexicon.
Speaker 1:Yes.
Speaker 2:And so perhaps it's a separate topic, separate time, but by and large I do not delay therapy for someone who needs it, even if they might be appropriate for a shingles vaccine.
Speaker 1:So now that you've got that patient in front of you, you know you've gone through kind of the whole spectrum of how this works. The box warning talked about some lab work, side effects. If you still have a patient sort of hesitant, what's your advice to a patient? Or do you really just kind of tailor to, obviously where their hesitation arises? But is there something that you commonly see that you have, you know, sort of a way to approach a patient to just make them feel better about going on one of these drugs?
Speaker 2:You know, oftentimes for patients with atopic dermatitis they're used to generally being pretty healthy that they had ever really been on big guns or systemic therapies in the first place, and so some of the reticence comes from there. For others, this is their next step after something they used and they're a little bummed that that particular treatment option didn't work, and so they're a little nervous about what if this doesn't work as well. I'd say, in all of these cases, to your point, you're going to be tailoring your conversation to the individual patient in front of you, but I like to remind my patients is look, this is one of the greatest times in history to have atopic dermatitis, and it's only going to keep getting better. I may not be able to tell you with exact certainty what the next few months looks like on this therapy, but I think this one gives you the best chance to meet your goals and my goals in terms of what we're trying to get to.
Speaker 2:We have the ability to see each other as often or as infrequent as you'd like, and even if this doesn't give you the best chance of getting better which it might, because this disease sometimes can be unpredictable we have a lot of other choices or combinations that we can try, and I think, something as simple as you, acknowledging the fact that sometimes we don't have all the answers, because atopic dermatitis is what we call a heterogeneous disease, meaning that immunologically it doesn't always behave exactly the same, unlike psoriasis, patients have a lot more buy-in because you know, if it was super simple, somebody would have taken care of their problem for them already and they wouldn't be here talking to you about using an oral JAK inhibitor.
Speaker 1:Fantastic. Well, you know, now that we know where JAK inhibitors are I know you mentioned just briefly in the future is if you could predict you know five years from now where we'll be for JAK inhibitors in dermatology. You know, I know you alluded to this a little bit earlier. Where do you think we'll be in this space with JAKs?
Speaker 2:I mean, it sounds like JAK inhibitors have the potential ability to touch up one of our common inflammatory diseases and even some of our less common ones too. So we're definitely, over the next few years, hopefully going to see some approvals for newer JAK inhibitors in other inflammatory disease states. So hydradonitis suppurativa I touched on is a big one with a few in development. Additionally, we're going to see some real approvals for vitiligo, which we've never had before, which is really helpful for people that may have extensive disease Additional systemic indications. We're going to be seeing JAK inhibitors for parigonodularis as well, a condition that we've really learned a lot more about over the last few years as we've had therapies available In our topical world.
Speaker 2:We're going to definitely see other inflammatory diseases with having a topical jack as an option. This includes milder elements of HS potentially. We saw some recent readouts for PN data, so maybe that's going to be an option for our patients. Potentially to some other indications whether you're thinking about certain types of scarring alopecias, maybe thinking about like annoyed diseases that I'd mentioned and others that we never really had treatments for. People are looking into that as well, and I also mentioned disease states that we never even thought about as disease states chronic hand eczema, which largely speaking has been a X us disease that we have not really fully recognized but are beginning to appreciate as something we see quite a bit. It's another heterogeneous disease that probably is going to benefit a lot with topical jack inhibitor inhibition.
Speaker 1:Wow, I mean, it's just truly exciting.
Speaker 1:You know, I think that's where I really wanted to bring you on, to help you know, not only our healthcare providers that listen, but just patients, because I think we need to get on the same page about this class.
Speaker 1:I think there's been a lot of fear mongering and just misunderstanding, and part of that is you know some of the studies, the labeling, but when you put it in context, like you just did, I think that it paints a much brighter future for these drugs obviously where they're going, but really where they are for the here and now and how they can benefit our patients, especially with atopic dermatitis. So thank you so much, Raj, for coming on and chatting with us today. I know a lot of people up there are going to feel a lot better about prescribing those JAKs and for those patients getting ready to take them, I think they're going to feel more confident in the drug as well and what it can do for them. For our listeners out there, if they want to find you, can you let them know where you're located online or elsewhere, if they want to track you down?
Speaker 2:Sure thing. So, first and foremost, thanks so much for having me on. It's been a real pleasure having, for having this conversation, one that I love having, and for anybody that wants to learn more. This is one of several disease-related areas I've probably been doing a lot of education on over the years. You can look for me on my various handles RajMDPhD on LinkedIn, where I like to share content that I've made on X as well, though not entirely active. I have my own webpage where I try to keep track of some of the stuff I've done as well. In case you want to pick up on that and it's literally rajmdphdcom as well, and just looking for me, we'll find my clinic page for our clinic that's located in Chicago as well.
Speaker 1:Well, thanks again, raj, it was great having you on the podcast, and for all of you out there, stay tuned for the next episode of Dermot Trotter, don't Swear About Skincare.
