DermInsider - VGR Session 4

Discuss the potential uses of JAK inhibitors in managing skin conditions

Identify key safety considerations when prescribing JAK inhibitors

Ask the Experts: All Things JAK

DermInsider - A Virtual Grand Rounds Series - Session 4: Ask the Experts: All Things JAK

Describe the latest clinical evidence for the efficacy and safety of oral JAK inhibitors in the management of alopecia areata (AA).

Identify appropriate patients with AA for oral JAK inhibitors based on AA disease severity 

Select appropriate dose adjustment strategies to optimize treatment of AA with oral JAK inhibitors

Review shared decision-making approaches to promote patient-centered care with oral JAK inhibitors 

FC24: JAK to the Future: Advancing Alopecia Areata Care with Oral JAK Inhibitors: An Online Activity

Describe the pathophysiology of itch in dermatologic conditions and how JAK inhibitors target the itch pathway

Outline the role of JAK inhibitors for the management of dermatologic conditions

Review key itch data for JAK inhibitors in skin diseases

Identify patients who would benefit from JAK inhibitors to manage dermatologic conditions

Baby Got JAK: Case Conversations on The Role of JAK Inhibitors in Dermatology

Evaluate data concerning side effects of JAK inhibitors

Assess new treatments and their on label and off label use

Understand the benefits of single use Negative Pressure Wound Therapy

Utilize novel skin grafting techniques in the clinical practice 

2023 Virtual Grand Rounds Session 16: December 6, 2023 - JAK Inhibitors and Wound Care Update

JAK Inhibitors

WEDNESDAY, Nov. 1, 2023 -- For patients with dermatologic conditions, Janus kinase (JAK) inhibitors are not associated with an increased risk for all-cause mortality, major adverse cardiovascular events (MACE), or venous thromboembolism (VTE) compared with placebo/active comparator, according to a systematic review and meta-analysis published online Nov. 1 in JAMA Dermatology.Noting that there is a current U.S. Food and Drug Administration boxed warning label for oral and topical JAK inhibitors regarding increased risk for MACE, VTE, serious infections, malignant neoplasm, and death, Jenne P. Ingrassia, from NYU Langone Health in New York, and colleagues examined the risk for all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions in a review of phase 3 randomized clinical trials with a placebo/active comparator group. A total of 35 randomized clinical trials, with 20,651 patients, were included, with a mean follow-up of 4.9 months.The researchers found that for composite MACE and all-cause mortality or VTE, there was no significant difference between JAK inhibitors and placebo/active comparator."We did not find an elevated risk of adjudicated composite all-cause mortality and MACE or VTE in patients treated with short-term oral or topical JAK inhibitor therapy for immune-mediated inflammatory diseases of the skin," the authors write. "It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient-level cardiovascular risk factors or are drug mediated."Several authors disclosed ties to the pharmaceutical industry; one author is a patent holder of resiquimod for the treatment of cutaneous T-cell lymphoma.

No increased risk observed for all-cause mortality, MACE, VTE versus placebo/active comparator in dermatologic conditions

Are Risks for Mortality, MACE, VTE Increased With JAK Inhibitor Use in Skin Conditions?

&nbsp;In this new installment of Tea with Dr. D, host James Q. Del Rosso, DO, is joined by Karan Lal, DO, to examine 3 complex cases where clinical reasoning required moving beyond conventional pathways. This episode features visually impactful case images that bring the discussion to life. The first case centers on an elderly patient on PD-L1 immunotherapy who developed erosive plaques on the head and neck. Dr Lal reviews the diagnostic challenges of atypical presentations, the limitations of standard treatments, and his decision to carefully introduce a JAK inhibitor with oncology support, illustrating the importance of balancing risks and benefits in drug-induced BP. Next, they consider a young adult male with diffuse hair loss. A biopsy confirmed androgenetic alopecia without inflammation, prompting Dr Lal to initiate low-dose oral minoxidil with finasteride. He details why combination therapy can be advantageous in younger patients, the need for counseling about shedding phases and time to response, and how to interpret prostate screening in those taking finasteride. The final case highlights a dramatic case of rhinophyma presenting as fibrotic nodules without classic inflammatory features of rosacea. Dr Lal explains his staged management of surgical debulking followed by laser resurfacing, along with the role of isotretinoin for long-term maintenance. For patients unable to pursue surgical options, he shares alternative approaches such as combining isotretinoin with neuromodulators to shrink tissue and improve appearance. Tune in to the full episode to see striking clinical images, learn how expert dermatologists navigate diagnostic uncertainty, and gain insight into creative, patient-centered strategies for challenging presentations

Karen Lal, DO

Tea with Dr. D

Tea with Dr D is Back Again! How Would You Have Handled These Cases?

In this episode of Cutaneous Miscellaneous, host Nicholas Brownstone, MD, speaks with Natasha Mesinkovska, MD, about diagnosing and managing alopecia areata (AA) with a focus on JAK inhibitors.Dr Mesinkovska shares diagnostic pearls, including full-body exam essentials, dermoscopy tips, recognition of key comorbidities, and the impact of AA on mental health. They also touch on less common subtypes such as diffuse AA and the ophiasis pattern, as well as the role of the SALT score.The conversation then turns to treatment, with insights into the 3 FDA-approved JAK inhibitors for AA: baricitinib, ritlecitinib, and deuruxolitinib. They discuss mechanisms of action, dosing, boxed warnings, and counseling strategies, while offering guidance on treatment selection and building confidence without head-to-head trial data.The episode closes with a discussion of GLP-1–associated skin considerations that may become increasingly relevant for board exams, along with key points on body contouring procedures that are seeing greater demand as GLP-1 use rises.Tune in to the full episode to sharpen your diagnostic skills, gain confidence in prescribing JAK inhibitors, and stay ahead on emerging board topics in alopecia areata and beyond.

Natasha Mesinkovska, MD

Cutaneous Miscellaneous Podcast

Hitting the JAKpot: New Frontiers in Alopecia Areata

In Episode 59 of Derms and Conditions, our host, James Q. Del Rosso, DO, continues his conversation with Christopher Bunick, MD, PhD, an associate professor of dermatology at Yale University School of Medicine who performs specialized research on novel treatments and therapies.&nbsp;

In Episode 59 of Derms and Conditions, our host, James Q. Del Rosso, DO, continues his conversation with Christopher Bunick, MD, PhD, an associate professor of dermatology at Yale University School of Medicine who performs specialized research on novel treatments and therapies. After discussing sarecycline for acne in part 1, the 2 switch gears to monoclonal antibodies (MAbs) and Janus kinase (JAK) inhibitors.Dr Bunick begins by discussing dupilumab, an IL-4 and IL-13 blocker with significant clinical efficacy and a favorable safety profile in treating atopic dermatitis (AD). He states that in a network meta-analysis, upadacitinib and abrocitinib were shown to be more effective at treating AD than dupilumab, but dupilumab was shown to be more efficacious than tralokinumab and lebrikizumab. Both agree that despite the similarity of many of the MAbs on cursory review, especially with the capability to inhibit IL-13, each agent needs to be evaluated independently due to structural, pharmacologic, and pharmacodynamic differences. They noted case reports where tralokinumab was effective and well tolerated in treating patients with inadequate response or problematic conjunctivitis with dupilumab. &nbsp;Next, they discuss IL-13 signaling in more detail, which is increased and more persistent in tissues compared to IL-4. However, Dr Bunick explains that IL-4 has more potent signaling, so IL-13 isn’t necessarily more clinically relevant. He notes that more research is required to further understand the structure-function mechanisms of cytokines within cells. He then mentions the noncanonical receptor, also called the decoy receptor, for IL-13, which may explain some differences in drugs that inhibit IL-13.Dr Del Rosso then addresses a very important recent publication by Dr Bunick and colleagues that evaluated adverse effects of special interest (AESI) of conventional immunosuppressive drugs as compared to 2 oral JAK inhibitors, upadacitinib and abrocitinib, used for AD. While the study population that used conventional immunosuppressives addressed a patient population beyond AD affected by more comorbidities, Dr Bunick notes that the risk of AESI also exists for these agents and is not limited to only JAK inhibitors. Dr Del Rosso agreed that many risk factors can contribute to AEs and not all the focus should be placed on JAK inhibitors. Tune in to this episode to learn important details about understanding and using monoclonal antibodies and JAK inhibitors!&nbsp;

Christopher Bunick, MD, PhD

Derms and Conditions Podcast

Improving Our Understanding of How Drugs Work: Clarifying Questions with Monoclonal Antibodies and JAK Inhibitors

In episode 15 of Cutaneous Miscellaneous, our host Nicholas Brownstone, MD, chats with Michael Cameron, MD, Assistant Clinical Professor of Dermatology at Mount Sinai and founder of Cameron Dermatology, a private practice in New York City.&nbsp;

In episode 15 of Cutaneous Miscellaneous, our host Nicholas Brownstone, MD, chats with Michael Cameron, MD, Assistant Clinical Professor of Dermatology at Mount Sinai and founder of Cameron Dermatology, a private practice in New York City.&nbsp;The episode begins with board review and practical tips on JAK inhibitors. Dr Cameron discusses the lessons learned from the ORAL Surveillance trial and focuses on safety of JAK inhibitor use in dermatology patients. He discusses how to counsel patients on the potential safety concerns with JAK inhibitors and offers his thoughts on what kinds of questions could be on the board exam concerning these novel therapies.&nbsp;In the main part of the episode, Dr Cameron provides his experience on starting his own private practice and gives advice on how to successfully start one.If you are considering starting a private practice or are just interested in hearing about the process, this is an episode you can’t miss!<a target="_blank" rel="noopener noreferrer" href="https://dermsquared.com/resources/biologics-and-jak-charts">FREE Biologics and JAK/TYK2 Inhibitors in Dermatology Quick Reference Chart</a><a target="_blank" rel="noopener noreferrer" href="https://www.hmpgloballearningnetwork.com/site/thederm/cover-story/jak-inhibitor-safety-what-did-oral-surveillance-really-teach-us">Dr. Cameron’s article, “JAK Inhibitor Safety: What Did ORAL Surveillance Really Teach Us?”</a> &nbsp;

Michael Cameron

Starting a Private Practice in Dermatology

In Episode 50 of Derms and Conditions, our host James Q. Del Rosso, DO, continues his conversation with Andrew Blauvelt, MD, MBA, a clinical trials investigator and former President and Owner of the Oregon Medical Research Center. Dr. Blauvelt has conducted almost 200 clinical trials on biologics and JAK inhibitors for the treatment of psoriasis and atopic dermatitis. While part one of this series focused on psoriasis, part two takes a deep dive into new therapies for atopic dermatitis.Dr. Blauvelt first discusses dupilumab and how this medication blazed the trail for the treatment of severe atopic dermatitis in patients with very limited options. Dr. Del Rosso clarifies the difference in mechanism of action between dupilumab and the newer drugs tralokinumab and lebrikizumab, and the two comment on how this impacts efficacy and safety. A common adverse effect seen with these drugs is eye related issues such as conjunctivitis and keratoconjunctivitis sicca, and they advise how to manage these conditions if they arise.Next, Dr. Del Rosso switches focus to the FDA-approved oral JAK inhibitors for atopic dermatitis, abrocitinib and upadacitinib. The biggest concern with JAK inhibitors has been their safety profile and black box warnings. However, Dr. Blauvelt discusses how these black box warnings came from a trial for tofacitinib to treat rheumatoid arthritis in a patient population featuring older patients with cardiac comorbidities that were taking prednisone and methotrexate concomitantly. This episode is full of clinical pearls for using the newest and most efficacious drugs for atopic dermatitis, so tune in to learn more!

In Episode 50 of Derms and Conditions, our host James Q. Del Rosso, DO, continues his conversation with Andrew Blauvelt, MD, MBA, a clinical trials investigator and former President and Owner of the Oregon Medical Research Center. Dr. Blauvelt has conducted almost 200 clinical trials on biologics and JAK inhibitors for the treatment of psoriasis and atopic dermatitis. While part one of this series focused on psoriasis, part two takes a deep dive into new therapies for atopic dermatitis.

 Andrew Blauvelt, MD, MBA

From the Research Center to the Clinic: Biologics and Other Systemic Therapies Part 2

You're listening to the Derms and Conditions podcast. Hello, I'm Jim Delrasso, and we have for a part two because part one was so fascinating. Dr. Andy Blaval, who is from Portland, Oregon. He's an investigator at Oregon Medical Research center in Portland. He was previously the owner and founder of this, but sold it recently. But he's still very active, and he's done a tremendous number of clinical trials. His main areas are psoriasis, atopic dermatitis, but certainly others, and has studied many biologic agents, systemic agents, primarily for psoriasis and atopic dermatitis. So, Andy, great to have you here. And the first conversation was fantastic. So I want to dive right into the second. What about atopic dermatitis? And the therapies that we have available now, we have monoclonal antibodies and Janus kinase inhibitors. Right. Jim, it's fascinating to me because we've had such an evolution in the psoriasis field and really not much happening at all in atopic dermatitis until recently. And so we had dupiliumab, also known as dupixant, approved several years ago now. And really, I consider that drug like a trailblazer. I mean, it was really an incredible advance. We had patients coming out of the woodwork, right, with such severe ad, and they just flowed into the trials. And Dupixent was just a godsend for so many people because those patients were stuck with cyclosporin, with methotrexate, phototherapy. It just really changed the field. It was interesting, Andy, you had the stepwise progression that happened in psoriasis, but it was a quick jump. We got spoiled in atopic dermatitis, right. We went from not having what you mentioned, which had a lot of problems and wasn't optimal of the systemics we had and just topicals to suddenly have this drug that was really, to use a modern term, a game changer. Right. Was a game changer, right. And people would say to me, well, oh, it's just like 2018 is just like 2004, when we started with embryo, and I said, absolutely not. I said, embryo is a good first step, but then we got so much better after that. Whereas dupixant, from the beginning, it was more like having a stellara. So for me, a really good drug from the beginning. And what we've seen is it's held up. It's really held up because it's been kind of tough to beat Dupixent in the last few years. So a bunch of people now kind of getting into it we have what I call dupy like drugs, and those there you have Tralo kinyumab, which is Adbre, which is a selective aisle 13 blocker. And then you have coming soon Lebri Kizumab, which is also a selective aisle 13 blocker that's probably going to be approved this summer, actually, 2023 summer. So those three are kind of working in similar ways. And then you have dupe four Nio 13. Right. Works in both types of receptors, one and two. Also, do you see any difference? What difference happens in terms of efficacy or safety when you're blocking I o four nio 13 versus just I o 13? Anything? Yeah, it's a really good question, Jim. And so back in the day, th one versus th two, and we only had kind of the two to talk about, il four was considered the prototypic th two cytokine. And so companies were trying to make il four blockers. And actually, way back when, there was an anti il four drug studied for eczema, and it didn't work. It actually didn't work and didn't go forward. But the whole Il four was kind of stuck with us and stuck with immunologists. And so when the makers of dupiliumab were working on that drug, they say, well, let's block Il four and aisle 13 another th two cytokine. And it worked. And really, what we think now, it's really the aisle 13 part of dupixent that works. It's really not much contribution to the aisle four blockade. And so that's why we're seeing now those selective aisle 13 blockers, because essentially we're getting comparable results as we get with duplimap. It sounds to me like, I hate to pick on Garfunkel, but it sounds sort of like Simon and Garfunkel. And I o four is Garfunkel, though he did have a couple of hits in there. Right? So he's showing up. It's important to have him there. But I o 13, I always thought of anti I o 13 as having more of a peripheral effect on skin as opposed to a central effect of some of the things that might happen in lymph nodes. But maybe I'm wrong about that. Actually, Jim, let me talk. Actually, there may be something to that because we see dupliumab approved for a number of other conditions. So it's approved for asthma and chronic rhinosinusitis with nasal polyposis, yasinophilic esophagitis. So these other sort of th two atopic manifestations we see dupab work in them, too. And so maybe in skin you only need 13 blockade, but sort of for asthma, maybe you do need that il four blockade because we don't have an asthma approval for those selective il 13 block. Right. And I believe trollchinumab was studied early on by another company, not the company that has it for asthma, and it didn't work that well, but it was a lower dose than what we're using now. So you still have a lot more to learn. And now we have the approval for. I almost said polyodoritis. No, dosa parigonularis. Excuse me, parigonodularis, even in patients that don't have any atopic background or atopic dermatitis. So diseases don't own the cytokines. Those cytokines can sneak up in other disease states, and I think we're learning that. But now we have Janus kinase inhibitors, so we have this array of monoclonal antibodies. We have two. Now we have dupixent and Adbre, as you mentioned, but we have Janus kinase inhibitors that are very effective for atopic dermatitis but carry some baggage that people get concerned about with safety. So can you walk me through that, how you decide on utilizing what agent and what you actually do? Monitoring. I don't get any baseline labs typically with dupixin, unless I'm expecting the patient may have something else going on. Do you get any baseline labs with dupixin or adbury? So you just asked a lot of things. Did. I'm excited, Andy. I can't help it. Okay, so I'm going to break that down a little bit. So first I'm going to say what are the commonalities between the biologics and the jacks? They both are linked to th two cytokines because those cytokines need to signal through the jax. And so they're both blocking Il four, IL 13, basically both types of drugs, and they're both getting at itch as well. So we know that the Il four receptor alpha is actually on neurons. It's on neurons. And so when we're using both types of drugs, the biologics and the jacks, we're actually blocking itch directly by blocking that neuron signaling. So it's really cool. And I think that's why we're seeing the prigonodularis incredible results is we're really blocking the itch rather than sort of getting at the disease. So that's really cool. And that's the link between these four drugs, the two biologics and the two jacks, is they all get at itch. Okay, so let's go to safety of the biologics. So we'll get rid of the biologics and talk about the jacks, adbri, and dupixent. 100% agree with you, Jim. They're very safe. There's really no blood test monitoring recommended with those drugs. The main issues are going to be conjunctivitis. Right. So eye disease, you get dry eye, you can get red eye, you can get swollen eyelids. I've kind of seen it all. Most of those patients are mild and manageable. And I always send to an ophthalmologist, by the way. But sometimes it's really bad, and you got to stop. You got to stop because the eyes get really bad. So I'd say for dermatologists, have an ophthalmologist in your back pocket, if you can, and send any dupixin adbree patients that have eye issues, send it to the ophthalmologist. Now, when I start those drugs, I often try to get patients just like we have atopic dermatitis patients moisturize their skin. I try to get them to use, like, an emollient for the eyes. There are several different products as a preventative. I don't know how well it works, but I haven't seen a lot of conjunctivitis with either of those two drugs to date. So I don't know how helpful that is. Do you do anything like that? Yeah, you're Lucky, Jim, because it's a pretty common side. You know anybody that has bad facial eczema or a history of allergic conjunctivitis where their eyes are runny a lot in the spring and fall, they're at risk for the dupey induced conjunctivitis in those patients. Definitely eyedrops. Just saline eyedrops is great. And then the main treatment for when it gets worse is just corticosteroid eyedrops that are used PRN. So not all the time, but sort of to knock down that inflammation. Right. What about the red face, that facial rash that we hear about? Well, I want to point out that conjunctivitis has been seen with both dupiliumab and trailicinumab. And in the PN trials, it was lower, but there was still some conjunctivitis. But some of those people, they did allow some people in that had mild atopic dermatitis. I don't know if they found only the conjunctivitis in the people with atopic background, I don't think they broke that down. But what about the transitioning now to Janus kinase inhibitors or switching to a Janus kinase inhibitor? We have abracitinib and we have eupatocytinib, Sabinco, and remvoke. Right. So can you walk us through that? All right, so both of these drugs are jack inhibitors, and they were both approved by the FDA for moderate to severe atopic dermatitis in January of 2022. So we have one year of FDA approval. And both of the drugs, what we're seeing is that is not a huge uptake, actually, in the dermatology community. And I think that the drug companies that make them are a little bit disappointed at the uptake. And for me, the elephant in the room, as you mentioned already, is the safety. Right. The safety of the Jax is kind of scaring, I think, a lot of dermatologists. It's the elephant in the room, because if you first will, first talk about efficacy, if you look at efficacy, they're terrific. They're actually, as a group, they're better than dupixin and Adbury, and it's one pill once a day and terrific efficacy, and it's fast. You see itch go away within a few days, and the drugs work fast. They're highly effective. So in terms of efficacy and quickness and working on itch, they're the best. But let me ask you a question right there, though, because if you look at how the trials were done, they used two different doses, but the FDA kind of tiptoed into it and set it up in the package inserts differently than how the trials were. Know, in the trials, a patient may have gotten one particular dose versus a higher dose. Right. They didn't start with one and then step up to the other. But the FDA, in the package inserts recommended with either one, whether it's Revoka, Sabinco, you start with the lower dose, and if they don't respond, go to the higher dose. Do you think that's really necessary from a safety standpoint? Because the higher doses work better, right. They definitely work better than the lower dose. It's a really good point. And thanks for catching me on that. I'm paying attention, Andy. I pay attention, but I'd still think they work better. So you have 15 milligrams and 30 milligrams of rinvoke, and you have 100 milligrams and 200 milligrams of sabinko. Okay, so you're right. In that, in the comparator head to head trials, they used the 30 of rinvoke and 200 of abro. So they used kind of the two higher doses and beat dupliumab. But if the 100 dose of Subinko and the 15 dose of rinvoke both work terrific as well. And so that is why the FDA has said, look, because of the safety issues, don't go to the high dose first. They say start at the low dose for both of those drugs and then only go to the high dose if you need it. And if you have good control on the high dose, go back down to the low dose to see if you can maintain control. But if you look at the safety data, is there you saving yourself potential adverse effects, the array of them, which we'll get into in a minute by going with the lower dose versus the higher dose, was there that much difference in adverse events in the two groups between the higher or lower doses of those two jacks? Yeah, you do see it. And actually you see it a little bit over time, but it's not a huge, it's not like a doubling. You don't see like a doubling of side effects with a double dose. You see an incremental increase. You see an incremental. Yeah, a little bit. And because of that, the FDA says, yeah, because you see a little bit more side effects with the higher doses. Let's try keep it on the low dose if you can. So let's get into, now you're deciding a patient, for whatever reason, is not responding as well as you would like with one of the monoclonal antibodies, or they got fatigue from it, they look tired of injections, whatever the reason is, or they just didn't respond that well, or they have really bad conjunctivitis and they can't get through that. So you're thinking about going to a jack inhibitor. What steps do you take, what monitoring do you do? And do you think there is a difference in the safety in the younger population that has fewer comorbidities, that were typically using them in atopic dermatitis versus patients that have used jacks for rheumatoid arthritis and other more severe disease, older patients with more comorbidities? A lot of question, but we're going to wrap it up with that. Okay, I'm going to take you step by step so doctors in private practice can understand jack safety. And Jim, I just got back from Hawaii Maui Durham meeting, and I spoke for 20 minutes on one topic on jack safety. So I gave a 20 minutes lecture, but I'm going to try to take it down to a few minutes to give you the highlights from that lecture. And so there are five boxed warnings for jack inhibitors. That's what everybody needs to know. And the five box warnings are cancer, heart attack and stroke, deep venous thrombosis, serious infections, serious infections and death. Okay, the bottom line is, and then the history, you have to know the history of where those boxed warnings came from, right? So they all came from rheumatoid arthritis studies in people with an average age of 62. There were 62 coming into the trial. They had to have heart disease to come into the trial. And 75% of the rheumatoid arthritis patients were on concomitant prednisone and methotrexate, and they were on a jack inhibitor called zeljans, which is a little more broad acting jack. So you have the creation of these five boxed warnings from trials done on another jack inhibitor in another population, and people who are old who, and people who are on prednisone at the same time. So that's where the safety warnings come from. And so I'm a little upset by it, because if you look at the safety data and the atopic dermatitis patients who are younger, right, the average age is in the 30s, they are not on prednisone or methotrexate, they're on monotherapy, they're on a newer type of jack that is more selective to jack one, and they don't have a lot of baseline heart disease risk. And so basically you have this whole different population with a different type of jack. And so what's happening in the ad data, three years now for both Sabinko and Rinvoc, is really only one of the five boxed warnings. Jim is really playing out for our ad patients, and that's serious infections. So we see a little bit of a signal. It's not huge, but there is a signal for serious infections. So jack inhibitors that we use in our eczema patients, yes, they can increase the risk of infection. It's not a huge thing, but we need to know that. And none of the other things are really statistically significant or above background levels. So even the venous thrombosis, the heart disease, cancer, basically none of that is playing out. So that's really good news, actually, for dermatologists. And I think they have to, I think, in my opinion, have to start to use Jax, because not only in ad, right, we've got jacks now in alopecia we got jacks in vitiligo. Jacks are coming for HS. And I really do think dermatologists need to get comfortable, really, with this class of drugs and kind of think of them as a possible infection signal and not worry as much as they should about all the other sort of warnings that are in the label. Well, think about it. Dermatology was, from so many years, a topical specialty. Occasionally, we would take out our prescription pad and write a systemic drug, tetracycline, toxicycline, minocycline. And when we had to learn about cyclosporin and even methotrexate, there was a learning curve for people there, too, because they're doing these blood tests for kidney problems or blood just. I think it's just going to take time. Andy, this has been fascinating. I want to thank you for joining us today, and I'm sure I'll be back to you in the future. And do me a favor. Say hello to your lovely wife, Molly, for me. She's a gem. Okay, Jim. Well, I really appreciate you asking me to do this and hopefully did some good with some folks out there that will help with patient care. That's the goal. Thank you. All right, take care. Thank you for listening to this episode of Derms and Conditions. If you have any questions or comments, please email us at podcasts at Fred Health. And most importantly, if you like this episode, subscribe to the Derms and Conditions podcast on Apple Podcasts or wherever you get your favorite shows. Thanks for joining us.

In Episode 33 of&nbsp;Derms and Conditions, host James Q. Del Rosso, DO sits down with April W. Armstrong, MD, MPH, Professor of Dermatology and Associate Dean at the University of Southern California and discuss&nbsp;the different members of the JAK family and how they enhance different intracellular signals.

In Episode 33 of Derms and Conditions, our host James Q. Del Rosso, DO sits down with April W. Armstrong, MD, MPH, Professor of Dermatology and Associate Dean at the University of Southern California. The two discuss the Janus tyrosine kinase (JAK) pathway and how JAK inhibitors have become a useful tool in treating several chronic dermatologic conditions. Dr. Armstrong notes that different members of the JAK family pair in different ways and therefore enhance different intracellular signals. In fact, these pairings are why certain JAK inhibitors are used for certain disease states and subsequently lead to a variety of adverse effects. Dr. Armstrong emphasizes the importance of knowing which JAK molecule the drug acts upon and the associated side effects for clinical monitoring. She highlights that one member of the JAK family, TYK2, can have a more targeted effect based on where the molecule is inhibited and therefore lead to fewer adverse effects. She discusses an example of a common case encountered in practice and some of the relative and absolute contraindications to starting a JAK inhibitor. You won’t want to miss these important pearls that can help you navigate this complex but exciting area of therapeutics. JAMES DEL ROSSO, DO FINANCIAL DISCLOSURES: CONSULTANT/ADVISOR Abbvie, Aclaris, Almirall, Amgen, Arcutis, Bausch Health (Ortho Dermatology), BioFrontera, BioPharmX, Bristol-Myers-Squibb, Cassiopea, Dermata, Dermavant, Encore, EPI Health, Evommune, Ferndale, Galderma, Incyte, JEM Health, Leo Pharma, La Roche Posay, Lilly (Dermira), MC2, Novan, Pfizer, Regeneron, Sanofi-Genzyme, SolGel, Sonoma (IntraDerm), Sun Pharma, Trevi, UCB, Verrica, Vyne (Foamix; Menlo) SPEAKER BUREAU Aclaris, Almirall, Amgen, Arcutis, Bausch Health (Ortho Dermatology), EPI Health, Ferndale, Galderma, Genentech, JEM Health, Leo Pharma, La Roche Posay, Lilly (Dermira), Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB, Verrica, Vyne (Foamix; Menlo) RESEARCH INVESTIGATOR Aclaris, Almirall, Amgen, Anaptys Bio, Arcutis, Athenex, Bausch Health (Ortho Dermatology), BioPharmX, Biorasi, Botanix, Brickell, Cara Therapeutics, Cassiopea, Dermavant, EPI Health, Ferndale, Galderma, Incyte, Leo Pharma, Lilly (Dermira), Novan, Pfizer, Ralexar, Regeneron, SolGel, Sun Pharma, UCB, Verrica, Vyne (Foamix; Menlo). APRIL ARMSTRONG, MD, MPH FINANCIAL DISCLOSURES: Research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

Fundamentals of JAK Inhibitors and What Makes Them TYK

Pearls in Managing Inflammatory Skin Diseases

Brett King, MD, PhD, and E. James Song, MD, delivered a comprehensive and practical session on inflammatory skin diseases, focusing on the evolving role of JAK inhibitors (JAKis) across multiple dermatologic conditions. Dr King began by outlining strategies for differentiating types of alopecia and optimizing therapy for alopecia areata (AA). He emphasized that patients may respond differently to various JAK inhibitors and that lack of efficacy with one agent does not preclude success with another. For AA, he recommended combining baricitinib with oral minoxidil and advised switching to a different JAKi if there is no regrowth after six to nine months at maximal dosing. He also reviewed data supporting the use of abrocitinib and tofacitinib for generalized granuloma annulare, drawing from open-label clinical trial results. In atopic dermatitis (AD), Dr King highlighted similar therapeutic nuances, noting that patients unresponsive to one JAKi may respond to another. Dr Song expanded on this discussion, focusing on managing partial responses to JAKis and strategies such as adding corticosteroids or dupilumab. He reinforced that nonresponse to one JAKi does not predict universal failure across the class. For AA, Dr Song discussed considering dupilumab as an alternative in patients with a strong atopic history or elevated IgE (≥200 IU/mL). Shifting to AD, he reviewed the latest insights on nemolizumab, approved for pruritus associated with AD, including emerging reports of dermatitis-type adverse events and recommendations for clinical use. He also discussed predictors of dupilumab responders and concluded with a look at tofacitinib’s potential role in unstable vitiligo, underscoring the expanding therapeutic landscape of JAK inhibitors across inflammatory dermatology.

JAK to the Future: Advancing Alopecia Areata Care with Oral JAK Inhibitors

This session explores the latest clinical evidence on the efficacy and safety of oral JAK inhibitors for managing alopecia areata (AA), including criteria for patient selection, dose adjustment strategies, and shared decision-making approaches to enhance patient-centered care.

How Should I Use JAK Inhibitors in My Practice

JAK inhibitors have exploded in the dermatopharmacologic market over the past few years, with myriad disease indications and formulations available. Raj Chovatiya, MD, PhD, started this vigorous session with multiple cases including atopic dermatitis, alopecia areata, and vitiligo, all well suited to treatment with JAK inhibitors. He postulated that the JAK inhibitors work well for numerous dermatologic conditions as, though they themselves are very targeted, the JAK family of proteins impacts many different downstream cytokines. For example, in alopecia areata, MHC Class I expression is increased through JAK 1 and JAK 2, and the activated CD8+ NKG2D+ cells release IFN-gamma, which binds on follicular epithelial cells leading to transition into the catagen phase. JAK inhibitors are perfectly targeted to interfere with the feedback loop that is perpetuated in this disorder.&nbsp; In addition, because they are small-molecule-based treatments, they do not develop immunologic memory like other biologics or theoretical tachyphylaxis. First-generation JAK inhibitors are ATP competitive, meaning they are less inherently selective and have a higher risk of adverse events while they target the highly conserved JAK H1 domain. First-generation JAK inhibitors include tofacitinib, baricitinib, ruxolitinib, and oclacitinib. Second-generation JAK inhibitors are also ATP competitive but are more selective. Conserved adverse effects include cytopenias, hyperlipidemia, and infections. The shared box warning for this class of medications was derived from a 10-year oral surveillance study of patients with rheumatoid arthritis on tofacitinib compared to those on TNF-alpha inhibitors. All of the patients were on methotrexate and many were over 50 years old with more than one cardiovascular risk factor. There was an increased incidence in opportunistic infections, major cardiac events, and malignancy. While this highly conserved evolutionary pathway is important in many pathways, including many that are not related to dermatology, adverse event rates seem to reflect underlying risk factors of the treated population. Dr Chovatiya emphasized the importance of knowing where the warning comes from and how to educate your patients on their own risk to decide if JAK inhibitors are an appropriate treatment. He finalized his talk by driving home the uses of the various FDA-approved JAK inhibitors. Ruxolitinib 1.5% cream is excellent for atopic dermatitis, simplifying complicated treatment routines, and vitiligo, especially in combination with NB-UVB. Abrocitinib and upadacitinib are approved for atopic dermatitis, while the latter has many clinical trials underway for other indications. Both of these JAK1 selective inhibitors demonstrated remarkable responses within 12 weeks of treatment. Baricitinib, a JAK1 and 2 selective inhibitor, was the first JAK inhibitor approved for alopecia areata in the US and is in studies for juvenile idiopathic arthritis. Ritlecitinib shortly followed baricitinib for alopecia areata. Lastly, deucravacitinib, the TYK-2 inhibitor, may be the superior oral option for patients with psoriasis.&nbsp;

JAK of All Trades: A Focus on JAK Inhibitors for Different Dermatoses

JAK inhibitors have flooded the dermatopharmacologic market with indications for many inflammatory dermatoses. Drs Golant and Del Rosso covered the physiology of this medication class along with important trials and safety data. As a quick reminder of the JAK STAT pathway, extracellular binding leads to JAK-receptor dimerization and phosphorylation of STAT proteins. Dimerized and phosphorylated STAT proteins translocate into the nucleus to activate target gene transcription. The dimerization of the JAK receptor is of particular importance as it is selective for a variety of interleukins and cytokines. While at high concentrations, JAK inhibitors likely would block all JAK receptors, they have selectivity: baricitinib is preferential for both JAK1 and JAK2, while abrocitinib and upadacitinib primarily inhibit JAK1 and secondarily JAK2.They moved on to review important trials on JAK inhibitors, like the MEASURE UP and JADE MONO trials, and the comparisons against dupilumab. Both doses of upadacitinib were effective in reducing EASI scores and, impressively, pruritus scores within 2 days of treatment in patients with atopic dermatitis. At 16 weeks, more than 60% of patients on upadacitinib 30 mg obtained an EASI 90 compared to &lt;40% of those on dupilumab monotherapy. In JADE COMPARE, which compared abrocitinib and dupilumab while patients were utilizing topical steroids, efficacy between dupilumab and high- and low-dose abrocitinib was similar. JAK inhibitors have been able to achieve more stringent endpoints for atopic dermatitis compared to dupilumab, which may alter our patients’ expectations of treatment response. &nbsp;Safety is an extremely important topic when discussing JAK inhibitors with patients considering the class-wide black box warning for mortality and major cardiac events. This resulted from a post-marketing study in tofacitinib use for rheumatoid arthritis patients. In atopic dermatitis, acne, headache, and nasopharyngitis are the main adverse events related to treatments. For older patients, there is an increased incidence of herpes zoster, and age-appropriate vaccination should be encouraged. Recommended labs include CBC, CMP, and fasting lipid panel, along with pregnancy, hepatitis, and tuberculosis screening at baseline. CBC, CMP, lipids and CPK should be rechecked every few months. &nbsp;

What You Need To Know NOW About JAK Inhibitors

Hi there. My name is Dr. Raj Chauvitia. I'm assistant professor of dermatology at the Northwestern University Feinberg School of Medicine. And it was really my privilege and joy to talk all about jack inhibitors. And the title of my talk, what you need to know now about Jack inhibitors, really highlights where we are in dermatology. We've seen a revolution of jack inhibitors across multiple different disease states that previously didn't have great therapy. So in my talk, we had a chance to cover a little bit about the history of where did Jackstat signaling come from? Why is it so important across so many diseases? And the fun part, what is happening across everything from atopic dermatitis and psoriasis to alopecia, areata vitiligo, even hydroadinitis supportiva. There is so much cool stuff coming, and even more headed our way. You just have to join me next year to hear all about what's happening.

Janus kinase (JAK) inhibitors are one of the hottest topics in dermatology today. In this session, Raj Chovatiya, MD, PhD, MSCI, reviewed the science behind JAK inhibitor therapy and the latest updates for JAK inhibitors on the market and in development. The Janus kinase family has 4 members: JAK1, JAK2, JAK3, and TYK2. These intracellular molecules play a central role in cell signaling for many different pathways. JAK1 and JAK3 play a role in immunity and metabolism, while TYK2 plays a role in immunity only. JAK2 has the widest range of influence, playing a role in immunity, metabolism, and hematopoiesis.&nbsp;Currently, there are multiple JAK inhibitors on the market for a wide range of indications. While each JAK inhibitor has distinct chemistry and is generally considered selective for certain JAK molecules, there is overlap and cross-talk between all JAK molecules, leading to class-wide side effects such as infection, cytopenia, and hyperlipidemia. All JAK inhibitors have received a black box warning from the FDA for increased risk of serious infection, malignancy, mortality, thrombosis, and major adverse cardiovascular events, except deucravacitinib which is an oral selective TYK2 inhibitor. Dr Chovatiya discussed these boxed warnings and recent evidence showing no relationship between upadacitinib, a JAK1 inhibitor approved for atopic dermatitis, and increased risks of major adverse cardiovascular events or thrombosis in the atopic dermatitis population.&nbsp;To conclude, Dr Chovatiya provided updates on the newer JAK inhibitors on the market. Ruxolitinib 1.5% cream, which is approved for atopic dermatitis and vitiligo, was found to decrease itch within 15 minutes of application in a Phase 2 open-label study. Upadacitinib is currently in Phase 3 clinical trials for hidradenitis suppurativa, with 38% of patients on upadacitinib 30 mg daily achieving HiSCR50 at Week 12 regardless of Hurley stage or prior TNF-a inhibitor use. Ritlecitinib, a JAK3/TEC inhibitor, and baricitinib, a JAK1/2 inhibitor, are both FDA approved for severe alopecia areata. Duration and severity of disease are inversely associated with therapeutic response, emphasizing the need for early intervention.

Boxed Warnings: What Do They Really Mean To You?

You. Hi, I'm Christopher Buenick, and I'm excited to tell you about the presentation I just gave at fall clinical 2023 in Las Vegas, Nevada. I was speaking about boxed warnings. Over the last couple years, there's been a big uproar in dermatology about how boxed warnings on the jack inhibitors used in atopic dermatitis have really affected our ability to prescribe these medicines, or really detracted from our confidence in prescribing these medicines for patients with moderate to severe atopic dermatitis. So what I did in my talk was I really tackled ten of the biggest myths surrounding box warnings that are out there, because what I wanted to do was to lay out a real rationale that dermatologists could use in understanding and communicating box warnings to their patients. I tackled several myths, and I'm going to summarize a few of them. First, I talked about the FDA in particular. What are the trends of how the FDA is applying boxed warnings? I talked about how the FDA may not always be consistent or logical in how it applies boxed warnings. I then took a deeper dive into understanding the differences between boxed warnings for over the counter medicines versus prescription medicines, because a lot of patients don't realize that some common over the counter, everyday medicines like ibuprofen have a boxed warning with some of the same adverse events as the jack inhibitors. So we talked about that. We dispelled that myth. We dispelled the myth that boxed warnings, they in fact do not mean do not use the medicine. And under the right context, absolutely those medicines should be used. And I covered all of that. But in particular, I stressed the fact that over 50 medicines in dermatology have boxed warnings. Dermatologists are really experts in prescribing boxed warning medications. We're very good not only in selecting the right patients to use these medicines in, but in educating our patients about those warnings and therefore using the medicines safely. Lastly, we talked a little bit about the safety rates of the jack inhibitors and how these medicines are actually proving far safer than we could have hoped a couple years ago when we first learned that there were boxed warnings on them for treatment of moderate to severe atopic dermatitis. So it was really a fun talk. I wish you were there. I hope that you are able to learn and gain something from this knowledge about the myths around box warnings and how when we dispel them, these medicines are very good for our patients and can change their lives when used appropriately. Thank you. Thanks much.

The approval of multiple novel JAK inhibitors for inflammatory dermatoses such as atopic dermatitis and alopecia areata has left many dermatologists wondering how to deal with the FDA-mandated class-wide black box warning. All oral JAK inhibitors carry a warning for serious infection, malignancy, major adverse cardiovascular events (MACE), all-cause mortality, and thrombosis. Christopher G. Bunick, MD, PhD, used this session to bust some common myths associated with black box warnings. Contrary to popular belief, a causal relationship between a medication and an adverse event does have to be established for a drug to carry a specific warning. FDA application of black box warnings is increasing according to Dr Bunick, so dermatologists should become comfortable discussing them with patients.&nbsp;Dr Bunick went on to discuss that medications with black box warnings can be purchased over the counter, as evidenced by ibuprofen, which carries a black box warning for cardiovascular thrombotic events and gastrointestinal events. There are many other medications commonly used in dermatology that carry boxed warnings, including TNF- inhibitors, isotretinoin, botulinum toxins, and multiple antimicrobials. To conclude, Dr Bunick reviewed safety data for JAK inhibitors compared with conventional immunosuppressives that have been commonly used for atopic dermatitis. A recent review found that both upadacitinib and abrocitinib have lower rates of malignancy, MACE, and thrombosis than methotrexate, cyclosporine, and systemic corticosteroids when used in patients with atopic dermatitis. Rates of malignancy, MACE, and thrombosis in patients with atopic dermatitis on JAK inhibitors are also equal to or lower than rates in patients with untreated moderate-to-severe atopic dermatitis.

Do you check baseline or intermittent labs on dupilumab or tralokinumab for AD?

You. When we're using the new systemic agents that are available for treating moderate to severe atopic dermatitis like dupilumab and more recently, trollkinumab, it's really not a need to check laboratory studies at baseline. These therapies work more along that th two cytokine pathway and even really more along what we would call almost an allergy type pathway, and they're not really considered immunosuppressive therapies. One comment I would make is that in the future, as we continue to elucidate different comorbidities associated with atopper dermatitis, for instance cardiovascular disease, our thoughts may change on that. And so I don't think at this point, all of us would agree that laboratory testing is not required for the injectable agents of dupliumab and trilogyumab.

What is the best treatment for lichen planus pigmentosus?

You. We're often asked about a condition called lichen planus pigmentosis, which is essentially a form of lichen planus, where there are pigmentary disturbances, where patients have these brownish gray or blue slate gray magules and patches that primarily occur somewhat in sun exposed areas, particularly on the face, the forehead, especially sometimes the cheek, and along the posterior aspects of the neck, is quite common. It's extremely difficult to treat, but we do have a host of therapies, not that any of them are FDA approved for this disease, which is a subtype of lycamplanis, but we can use, initially, topical corticosteroids. I personally will rotate topical corticosteroids with other agents that are important even as monotherapy for treating these patients, such as topical calcium neuron inhibitors and as well, the newer generation Janus kinase inhibitors may play a role in the management of disease states like lichen planus, and therefore are slowly being used in the setting of lichen planus pigmentosis. Finally, we can use some oral therapies sometimes as well. Agents like oral dapsone have been used, ac tretin have been used, and finally, I will conclude with mini dose, 30 milligrams once a week, exocarin, which you know, is an anticoagulant therapy and that has been studied in some very, very small anecdotal trials for the management of lichen planus pigmentosis. Of course, you'd need to make sure that those patients are wearing sunscreen all the time so that their conditions does not worsen.

Roflumilast vs tapinarof - which is more efficacious?

You. We have two new agents to treat all spectrums of psoriatic skin disease emflumalast, a phosphodiesterase four inhibitor, and to Pinarov, which is an arrowhydrocarbon receptor agonist. We really don't know which one is stronger than the other because they've not been compared in the clinical trials. Nevertheless, it's probably more important to tell you about the benefits of really both agents. The phosphodiesterase four reflumilas in clinical trials was successful not only treating localized skin disease but also intertrogenous folds. So that's unique about that phosphodiesterase four inhibitor. And it's a highly concentrated form of phosphodiesterase. So it's not your grandmother's opde four inhibitor. And for topinorov, which is an arrowhydrocarbon receptor agonist, it has some unique properties in it down regulates th 17 cytokines, hence its benefits in psoriasis and also th two cytokines, where it may be effective, as it is in clinical trials for the management of atopic dermatitis.

Can tapinarof be used in pregnant patients with psoriasis?

We're often asked about the use of various topical therapies, including some of the newer topical therapies for the management of a variety of diseases and, for instance, a drug like topinorov. In the setting of managing all spectrums of psoriatic skin disease. The use of topinorov is not recommended in the setting of pregnancy nor lactation, and the reason is, is because it really has not been studied.

Do you recommend getting the zoster vaccine before starting a JAK inhibitor?

You. When considering the use of an oral Janus kinase inhibitor, for instance, whether it be for atopic dermatitis with abracitinib or upatocytinib, or the use of baracetinib, which is recently approved for alopecia areata. It's my recommendation anyone above the age of 50, an adult that's above the age of 50 should get the shingles vaccine. Specifically, I would recommend the shindrix, which is about 90% effective. And always getting vaccines ahead of time is ideal. But because it's a killed vaccine, in principle, it could be given at the time that one is initiating this. As we always like to say, live vaccines should be administered before any immunosuppressive therapy. In this particular case, it's a killed vaccine. The challenges that we find as well, too, is that it's not just a one dose vaccine, it's a two dose vaccine that's given at baseline and two months later. But again, it is possible that in a pretty urgent situation where you have to treat your patient and get them on therapy because they're significantly flared, you could have your patient have administered the shindrix vaccine accordingly. So, yes, let's administer that to individuals that are 50 years of age or older ahead of time.

Do new topicals address underlying systemic inflammation?

You. There are a number of new topicals that have recently been approved in just this last year for the management of atopic dermatitis ruxalitinib, 1.5% cream that you can use twice daily to manage patients with mild to moderate atopic dermatitis. We also have brand new approvals in this past year for individuals across all spectrum of psoriatic disease. Topical therapy S with a PDE four inhibitor of rafumalast and also an arrowhydrocarbon receptor agonist into Pinroff. These agents all work locally. Their systemic absorptions is really minimal, so their impact on systemic inflammation would not be likely. But nevertheless, what's important is that they work locally, that they decrease inflammatory cytokines locally, really, all of them. So ruxalitinib in the setting of mild to moderate atopper dermatitis and for all spectrums of plaque psoriasis, refumalast down regulating phosphodiesterase four and topinorov agonizing or upregulating the arrowhydrocarbon receptor. What's interesting about topinnov is it also restructures the skin barrier because it does increase a variety of proteins that are important in the barrier restoration that is required when we're managing individuals, for instance, with atopic dermatitis. Although the drug is not yet approved for atopic dermatitis, it is being studied for such and.

Any concern using topical JAK inhibitors in patients on dupilumab? 

When we're using agents for patients with moderate to severe atopic dermatitis, like dupliumob and even trailokinumob, the addition of a topical genus kinase inhibitor actually makes perfect sense. Now, the disclaimer is that those are off label uses on both sides. When we have dupiliumob, it really is on label, or for childocinumo, we wouldn't necessarily, from the package insert, use this. But I think most of us in clinical practice feel like there are different mechanisms of action and there is collaborative impact on downregulation of very important th two cytokines, like interleukin four and interleukin 13. And I think that we get a reestablishment of the skin barrier not only from utilizing the systemic biologic therapy, but also the improvements that we get from using a localized topical therapy. And we avoid some of the consequences that we would get from using concurrently a topical corticosteroids, as was done in the clinical trials. For instance, dupiliumab.

If a patient is on long term prednisone from PCP for refractory AD can that patient also start a JAK?

When patients are on prednisone and we're about to start a Janus kinase inhibitor, and particularly if they're using it for, let's say, recalcitrain atopic dermatitis or they have asthma in the background, we certainly do not want to stop their prednisone abruptly, and it's my recommendation. I think my colleagues would agree that we wean it off slowly, but we can start the Janus kinase inhibitor right away.

Are IL-23 blockers as effective as TNF and IL-17 blockers at preventing the progression of PsA? 

You. The interleukin 1223 and the newer interleukin 23 blockers in their FDA approved dosing regimens actually do not inhibit radiographic progression of joint disease in psoriatic disease. Nevertheless, for example, an agent like gucelchumab in a different off label dosing regimen of 100 milligrams every four weeks. As you know, the standard dosing regimen is every eight weeks after a period of induction of zero week four, and then every eight weeks thereafter. The four week dosing regimen does demonstrate a radiographic inhibition of disease. In general, the class of 1223 and 23 blockers as well, do perform adequately in axial disease. But I think it's pretty clear from the literature, sure, that interleukin 17 blockers and our original TNF blockers appear to perform somewhat better in the management of the axial disease components of psoriatic arthritis.

JAKs and TYKs - What You Need to Know

You. Hi, I'm Dr. Neil Batia from San Diego. During the meeting, I had a chance to talk about Janus kinase inhibitors, specifically making the distinction between jack inhibitors and tick two inhibitors, or tyrosine kinase two inhibitors. We talk about some of the disease states that are very useful for this class of drugs and some of the conditions where patients are achieving really quick results as well as good long term safety. My biggest top think was also not to worry so much about black box warnings, because the adverse event profiles that we saw in the trials actually don't match the severity of what was in the old days where black box warnings were developed. Even more so, again, making the distinction between the molecules and the targets and of course, some of the new drugs that are in development and where their potential targets are dermatologists. Everybody are going to have good opportunities to get patients better. We've seen the NRS data within three days of patients with atopic dermatitis, and I think we really have some good opportunities to get patients better for the long run.

In the ever-expanding world of systemic dermatologic treatments, busy clinicians may struggle to keep up with all of the recent approvals. In this session, Neal Bhatia, MD, provides an in-depth look at the efficacy and safety data of several Janus Kinase (JAK) inhibitors for a variety of inflammatory diseases including psoriasis, atopic dermatitis, alopecia areata, and hidradenitis suppurativa. Dr. Bhatia begins with an overview of the mechanism of action of JAK inhibitors as well as their safety profile and how to address the dreaded black box warning. He also highlights the increasingly common side effect of acne, colloquially known as “JAKne”. For upadacitinib, 13% of patients on the 15 mg dose and 17% of patients on the 30 mg dose developed acne, which was mild in two-thirds of cases. For abrocitinib, 2.9% of patients on the 100 mg dose and 6.6% of patients on the 200 mg dose developed acne that was mild to moderate in all cases. For baricitinib, 2.9% of patients developed acne across all doses.Next, Dr. Bhatia reviews efficacy data from several pivotal trials. He starts with upadacitinib and its quick onset. By week 2 of the Measure Up 1 and 2 phase 3 trials, 38% of patients experienced EASI-75 by week 2. With regard to itch, 16% of patients experienced a numerical rating score (NRS) improvement of at least 4 points by day 2. This is important because breaking the itch-scratch cycle earlier than biologics leads to improved quality of life much quicker. In the abrocitinib phase 3 pivotal trials, 62.7% of patients on the 200 mg dose and 39.7% of patients on the 100 mg dose achieved EASI-75 at 12 weeks, compared with just 11.8% of patients on placebo.Dr. Bhatia wraps up the session highlighting several medications that are in the pipeline as well as off label uses. This includes Jaktinib for atopic dermatitis, rilzabrutinib for atopic dermatitis and pemphigus, ritlecitinib and brepocitinib for alopecia areata, and deucravacitinib for lupus.

Do you compound any currently available JAK inhibitors into creams for topical use by your patients?

You? I do. I recommend typically topical topacidinib, which we have mixed up in a 2% topical ointment, and we use it for our alopecia patients. I haven't found it to be greatly successful on the scalp, but in my patients with eyebrow involvement, we sometimes do find that it can be very helpful. I've had a few patients who've used it for vitiligo, and again, it's usually the topical topacidinib. I have compounded ruxalidinib as well, but that's a little less commonly used and a little bit more expensive, in my experience. So I've used topacidinib, the topical topacidinib, and that's worked out pretty well for patients. There are some people who feel that the mixture where I've been compounding it is a little tingly when they put it on, but it kind of goes away very quickly, so people tolerate it quite well.

What are the recommendations on how to monitor patients on oral JAK inhibitors?

You. A very common question is what are the recommendations on how to monitor patients that are on oral Janus kinase inhibitors, specifically with laboratory testing? I want to refer you to an article by Nash in the Annals of Rheumatic Diseases in 2020. And you can go to PubMed, it's open access and you can actually print the article. And there are recommendations from clinicians that utilize a lot of Janus kinase inhibitors because these agents, although they're not yet approved in the United States for dermatologic disorders, there are many of them that are used for other conditions in other specialties, like in rheumatology, for example. So patient selection is important. So in the history we want to get the vaccination status of the patients, if they have any history of severe infections or malignancies, if they have any history of thromboembolic disease. And then as far as pretreatment screening, we look at obviously getting the history and physical exam, as I mentioned, but looking at complete blood cell counts, liver function tests, hepatitis B and hepatitis C testing, TB screening and HIV testing in patients at high risk. Those are important as far as baseline evaluation because, remember, these agents, depending on what Janus kinases they're inhibiting, can impact on a variety of different organ systems in terms of potential adverse events, even though they may be uncommon in many cases. Then as far as follow up monitoring, complete blood cell counts and liver function tests at month one and three, and then periodically there after around every three months, lipid levels at about three months and maybe periodically thereafter. And don't forget, skin examination, annual skin exams and skin cancer detection are recommended. So this article really gives you a good framework until we get further direction as we see approvals and recommendations in package inserts and from further information from studies.

Do you prescribe oral JAK inhibitors for your pediatric patients with vitiligo or alopecia areata?

So the answer to that is that I have not yet prescribed oral jack inhibitors for any of my pediatric vitiligo patients. I have prescribed it for my adult vitiligo patients, and in those situations I've used oral tofastidinib, and I do prescribe oral jack inhibitors for my alopecia. Pediatric patients who are over 16. I haven't gone less than 16 yet, and again, I use the tofacidinib and it's five milligrams twice daily. I do have several patients who are in open label studies taking oral jacks, and unfortunately, none of those are pediatric trials, so I can't comment on that. But certainly in my pediatric patients, again 16 and over, we've had good success using the oral tofacidinib in many of those patients, and they tolerate it quite well.

Do you need to monitor any laboratory testing with topical JAK inhibitors?

You. A common question we receive is, do you need to monitor any laboratory testing with topical Janus Kinase inhibitors? We certainly know that there are recommendations to date, and we'll see what happens as these drugs get approved for dermatologic conditions given orally, we know there's laboratory monitoring and involved. However, the data we have, and I've been involved with some of these studies with topical application of the Janus kinase inhibitors do not appear to elicit any of the systemic safety signals that we see with systemic administration. So in my mind, I don't believe you need to do laboratory testing. Some clinicians may want to do it because these agents are new, and as they get approved, we'll see what the FDA puts in the labeling, but we certainly don't see the systemic reactions with topical application that have been associated with these agents given orally. Depending on what Janus Kinase inhibitor you're giving.

How do you get oral JAKs covered by insurance for alopecia areata?

How do I get jack inhibitors covered by insurance? Boy, if I had an answer to that question or had a way to fix that, I think I'd get all the referrals from around the country. I don't have a great answer. Most of the time I get these for patients who are willing to pay cash. I have been able to get oral tofacitinib as compassionate use for some of my patients. Remember, it is approved for rheumatoid arthritis. So if you do have a patient who has uncommon at RA and vitiligo for example, which isn't uncommon, talk and coordinate with your rheumatologist buddy. See if you can get it covered through the RA indication because it is on label for that. Also, the topicals fairly inexpensive depending on which compounding pharmacy you use. So that's something to keep in mind.

Should we consider the JAK inhibitors more broadly immunosuppressive than the biologics?

You. A lot of clinicians have questions about how immunosuppressive are Janus kinase inhibitors compared to some of the biologic agents that we use, whether it be dupiliumab or il 13 inhibitors that are coming along for atopic dermatitis or some of the injectable biologics that we have for psoriasis. You really have to look at the specific Janus kinase inhibitor and look at what Janus kinases are being inhibited, realizing that even if they're selective, there may be some spillover into other Janus kinase enzymes being inhibited. And then you have to look at what's downstream from that Janus kinase stat signaling, what the end effect is, because there are many different cytokines and mediators that interact with different Janus kinase inhibitors, and they have different implications in terms of what they signal downstream. So, for example, if you're inhibiting Janus kinase one, you're going to have a modulatory effect on interleukin four, interleukin 13, interleukin two, interleukin 615 22, 31, interferons, some of the interferons and TSLP, thymic stromal lymphopoietin. So you have a broad inhibition or modulation of the effects of those different cytokines. So in general, yes, Januskinase inhibitors are more modulating of the immune system than targeted antibodies that affect specific, but you still have to look at each individual case.

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