Eric Simpson, MD, MCR

I agree with you and that tells them you're now on their side, which is wonderful. We have this future of research, and is there something that you're most looking forward to in terms of clinical research, or something in the pipeline, or something that we need, or you'd like to see? Raj, is there anything in the future that you're kind of excited about?

 Yeah. One of those holy grails of any inflammatory disease, and atopic dermatitis in particular because of how heterogeneous it is, is how can we take someone that comes to us on a first visit within a few minutes of just talking with them, understanding their disease, to figure out what is that best treatment choice for them going to be for what is their burden? When you have so few targeted treatment options, the answer is kind of easy because you go with the 1 or 2 that you have, but as we're going to see, this explosion over the course of the next decade with phase 1, 2, 3, and launch is actually happening, I'm excited about how we're going to combine that amazing clinical genotyping data that has sort of been a pioneer over the past decade or 2 along with some of the cool work that's being done in trying to figure out good biomarkers when it comes to everything from gene expression to protein expression to serology, and putting that together in a package where I can tell my patient, “this is going to be the treatment that I know is going to get you to this point of clearance better than anything else out there.”

Wouldn't that be wonderful. Alexandra, any thoughts on something that you're looking forward to?

: Yeah, the concept of being able to easily and predictably personalize how we pick treatments in any inflammatory skin disease does feel like the holy grail. Overall, with the approach to the patient with atopic dermatitis, I look forward to seeing that continue to change because these patients have been undertreated for quite a long time. While that has changed over the last, let's say 5 years or so, we still have work to do capturing the more moderate patient and getting people that sometimes were lost to follow up back into the office and getting them clearer. I look forward to seeing that change and look forward to new therapeutics. There are exciting areas or therapies on the systemic side that may indeed be disease-modifying or modify the disease at the course somehow or lead to longer periods of patients being disease-free.

That is exciting. Eric, what are you most excited about?

: Yeah, I'm going to go with the International Eczema Council who said that this ability of treatments is to change the natural course of comorbidity. My research career has been dedicated to primary prevention trying to prevent eczema in general, but this secondary prevention idea is something I'm really interested in. And we've all seen it, both topical and systemic, especially in our pediatric cohort that if we can control the disease for long enough and keep the disease state quiet, that may change the natural course and patients may not need treatment later on. There are some very recent studies, especially in Japan, that show how dermatologists can make a difference in that even in their allergic comorbidity. There's some data from Japan in that aggressive treatment in patients who get that proactive approach early in their AD career that they can prevent food allergy at 2 years of age. At the interfaces of when a patient comes in, we could do something that will change the course of their life, and prevent the need for medication and prevent comorbidities in the future. I'm interested in that from a topical approach and a systemic approach.

We have a lot of exciting, hot topics that we're looking forward to on the horizon. I'd like to thank my colleagues for joining us and I'd like to thank all of you for this very informative discussion. Thank you for watching this HCP Live Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right in your inbox. Thanks so much.

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Raj J. Chovatiya, MD, PhD; Alexandra K. Golant, MD; Eric Simpson, MD, MCR; and Linda Stein Gold, MD, share clinical pearls and discuss the future treatment landscape for atopic dermatitis.

Future Directions for Atopic Dermatitis Management

This was a great overview on how to practically approach these new treatment options. At this point, we have so much of a challenge getting these patients under control and keeping them under control. You all have so much experience with atopic dermatitis patients who are mild, moderate, and severe. Do you have a particular tip either for getting that patient under control, or maintaining control? Is there anything in particular that you've learned over your experience that you can pass along that is something that's really helped your patients?

: Focus on having patients recognize and accept that we have no cure for this disease. I don't foresee in the near future that we're going to have a cure for this disease, but that is how lucky we are to be where we are in 2022 with a number of different treatment options and the ability to get patients clearer than they were before, both on the topical and system. I like to set that stage. Patients approach their treatment with a lot of optimism and a lot of hope. For topical patients, trying to get patients on board with, or proactive maintenance where they're not just treating acute flares for a week at a time and stopping then waiting until the next acute flare happens, is very important, especially for the children with atopic dermatitis and getting out of that mentality that we know that there is inflammation that persists between these flares. For systemic patients, trying to get a sense of what drives their disease suffering and personalizing the treatment to that is the concept for the systemic eligible patients who have lived with this disease for so long, sometimes that they cannot imagine their life without the itch or without their AD driving the narrative of their life. Setting the stage that there is a series of events that can make that possible for them has been powerful and important in leading them to the right treatment.

Our patients underestimate their age significantly because they don't remember what life was like.

Raj, do you have something that you've learned over the course of your career that you can help others to get better control?

There is a lot of power in the patient voice and what they say about their atopic dermatitis. It's one reason why I'm such a huge fan of numbers, particularly when it comes to patient-reported outcomes. If you can find a way to sneak in a couple of these into your encounters, you can find a way to help keep your patients understanding that you used to be this bad by your own words and now, you're here. Sometimes people are like, “I don't know if I'm better or not,” but they can't argue if it's your own impression, so just ask them, “how severe do you think you are? How well have you done on this therapy and how bad is your itch or pain?” Things that are even outside of an academic setting, where everybody has 3 hours to see a patient like Eric, just simple questions, each one takes a few seconds, and you can get valuable information from the answers. Somebody that may be on the ledge like, “I don't know if this treatment's working,” they're going to feel remotivated and rejuvenated. They might say, “I used to have a 10 out-of-something itch and now I'm down to a 4. You're right, this is working. Let's keep doing it.”

Keeping it easy… If people had to do an easy score at every visit they would go crazy, but simple things like “how bad is your itching? Did you sleep last night?”

 I love doing the easy scores. In general, easy stuff like that just takes a few seconds to do is so easy to implement. More importantly, you can just look back at that last note and have a good point of comparison.

Eric, you've had a whole career in atopic dermatitis. Can you whittle it down to maybe a key tip that you can give us a takeaway tip?

: The proactive approach is extremely helpful meaning treating normal skin. Once you've cleared it, let's say with topical steroids and using a nonsteroidal to normal skin. Now, we don't have the data in our topical JAK inhibitor on proactive treatment. I would reserve that or document if you're going to use a JAK inhibitor topically for proactive treatment. I do think it will work, but we need to see some studies and some absorption data to safety data, but it is a highly effective approach to keep people clear. On the systemic side, I completely agree with my colleagues. I'd say the only tip is if, when you're trying to make that connection with your patient, I have found that discussing or acknowledging you've probably been told by many physicians and family members to just stop scratching. I would say this is not your fault and to put your guilt aside because you didn't do this to yourself and you can't help it or stop the scratch. I know it feels good, but put that aside; you have a reflex and that's not going to make your disease go away. You did not cause this. When you start talking in those terms, it's amazing how many people carry this idea that they're causing it themselves and just stop scratching it. They're like, “ok, this person is my ally, they get it, and they understand it.” The more you can be a team, the more it helps everything from then on.

I agree with you and that now you’re on their side, which is wonderful.

Alexandra K. Golant, MD; Raj J. Chovatiya, MD, PhD; and Eric Simpson, MD, MCR, discuss challenges adolescent and adult patients face with current oral and topical therapies and optimizing disease management.

Patient Challenges With Available Therapies for Atopic Dermatitis

With your experience thus far with the JAK inhibitors, has your experience been positive? Do you feel like they're living up to, both orally and topically, what our expectations were? Where are they over-excelling? We talked a little bit about itch. Alexandra, do you feel like you use them? Do you use them as monotherapy and feel that this is where they're most successful? Do you use them with steroids? Everything, especially the topicals, is studied as a monotherapy. They tell us we shouldn't be using it with other agents. Are you doing that in real life? What's going on?

: For the systemic JAKs and for systemics in general, whether you tell patients to use or not to use topicals, often people will supplement or the systemic JAK inhibitors are so fast-acting that oftentimes the topicals get dropped quite early if they are on board at the beginning. If you look at their concomitant topical steroid data, they barely got a boost because most patients are well controlled with monotherapy use. I like to get a clean picture of what the drug is doing on its own. I usually say, “we're going to start this new medication and let it behave on its own.” The itch improvement in particular happens so early that I don't think people are reaching to the supplement with many of their topicals for the majority of patients. The topical JAK inhibitor is somewhat different and patients are not always reaching for it if they're having an acute flare, but more for maintenance or proactive maintenance. The majority of time it is being used as monotherapy or in some type of alternating basis with a low to medium potency topical steroid.

You have no problem giving a patient both topical steroids. Raj, do you give patients more than 1 prescription potentially?

 Yeah, sometimes you're forced to. It hurts me on the inside to contribute to polypharmacy because by definition it is anywhere from 2 to 11 prescription medications. When you think about it as dermatologists, we're committing that cardinal sin constantly because we can't go a visit without giving 3 to 4 things. I'm as big of a culprit as they come. The nice thing about these new therapies is that we're able to simplify the regimen and we always talk about this step-up additive approach, which is something that we've been trying to talk about, that is now a step-down simplification approach. If you're moving up to a higher step therapy, the data would reflect that you're not going to get that much of a boost from concurrent topical corticosteroid use in the case when oral JAK inhibitors since they can largely work on their own. When you look at that phase 2 data compared to triamcinolone with topical ruxolitinib, it's doing more heavy lifting. You’re probably not going to get that much more additive benefit over something that’s going to be maybe as, or even less potent. With many of these new medications, as we start to get familiar, I'm trying to work them in as monotherapy, but only in the circumstances that require it to add on a normal topical anti-inflammatory. Over the course of the next year or 2, this is when most of our real-world data and reports are going to start to come out; what does a real-world prescribing pattern look like? How are people combining these therapies? How are people not following the exact indication? It's going to give us a good idea if there's any safety or efficacy signals that we just weren't clear about before.

What has your experience been now that these drugs are available with blood monitoring? Are your patients pushing back? Do you feel like clinicians are pushing back, or do you feel like this is ok and that we can do baseline labs? Do you have an established routine at this point in terms of what you feel is the appropriate blood monitoring? Alexandra, what do you do?

: I had that same question myself when I was counseling patients on the laboratory monitoring just out of curiosity on how it would be received. In the context of a medication that you've gone through the label with a patient on, there's some comfort that patients get in saying that there are these risks, but we are going to be doing laboratory monitoring with the exclusive goal to make sure that you're staying safe on this drug. I have not received any pushback on the laboratory monitoring. I am doing baseline labs and bringing patients back between that 4- and 6-week mark to check labs again and plan to see them once these just came out end of January. No one's at that past that second visit. But again, around week 12, we'll recheck the lipid parameters that is per the label and then we'll do labs between every three and four months after that. Though, it's definitely still a work in progress for me. I welcome others’ input, too.

I agree with you and I'm wondering, Eric, do you have this down to a science at this point? What are you doing?

: I do not. There are some subtle differences right in the package insert. For example, with upadacitinib, they say to check lipids at 3 months and that's recommended from the FDA and then check as needed thereafter. Whereas axitinib does have a small percentage of patients who can reduce platelets at 4 weeks and that's less than 5% of patients. The recommendation is that you check a CBC at 4 weeks after use. I'm going to have a consensus paper of, how can we just make this simpler and not worry about all of the individual details? If you wanted to not do that, I check at 4 weeks, redo the labs at 4 weeks, and probably redo them at 3 months for now. If everything's normal, we're all going to have different frequencies and so we need more real data. After 3 months, if nothing's wrong, you could go every 3 months or maybe even every 6 months potentially after that.

I want to come back to that and check the lipids at week 4. Are you doing a baseline?

Why is it not in the label to do a baseline? How many people walk in and have abnormal panels at baseline? If you're doing a disservice and if you don't know who the patient is when they come in, did they have a problem at baseline or not? Even though it doesn't specifically state it, that's critical to do.

Raj, any other thoughts on this? This is one of the things that people are going to have the most questions about. Am I doing it right? When can I stop?

Yeah. Some degree of hesitancy about the adoption of a new therapy sometimes comes from the other stuff you have to do aside from just prescribing. Back to psoriasis for a second, let's take it back to not that long ago to the days of TNF blockers, right? Largely, there are a lot of similar overlaps into some of the things you're doing at initiation. Some of the things you're looking at in follow-up. Many of those patterns just fell into place, become commonplace, and people got comfortable with it. We are largely saying the same thing. You're probably going to check a little more often early and later on, you're going to check a little less often. If you just want to break it down at the beginning, you're going to do a little bit of ratters manufactures stuff and beyond that, it's going to be the kind of labs we're very used to. When you put it in a big picture like that, it's not that different from monitoring that we've become comfortable, whether it be conventional oral immunosuppressive agents, or whether it be biologic therapies for other inflammatory diseases. I don't have too many differences in terms of what everyone here has very nicely said that they're going to do, but taking a nice big picture view of it about what else have we done with inflammatory disease over the past 2 decades will maybe make people feel like this isn't some weird foreign thing. It's actually quite familiar to what we've done before.

We have so many great choices right now, if a patient comes in and they're in that in-between category, where could we potentially use a good topical, a topical JAK, an oral JAK, or a biologic? What's going to make you decide and push you to one direction versus another. How do you decide?

: It's important for the clinicians to know that the indication has some wording in that. It makes it sound as if the indication is that if they're a systemic candidate and they failed at least one other systemic therapy and the wording is a little vague and it's unclear whether they need to fail a biologic or systemic agent. As a clinician, you need to read that and then, be comfortable with how you interpret that so that you can defend that in your note, or if you are going to go straight to an oral JAK, for example, after 1 week course of prednisone and in your mind, that's trying another systemic. There might be some practice variation. To answer your question, I'm going to see this as a potentially second-line systemic and then it'll roll the patient preference. There are other biologics available other than dupilumab. Do you switch to a different biologic class? Do you go straight from a traditional immunosuppressant to a JAK inhibitor? It's going to be patient preference and their risk aversion, their comorbidities, and all of that. I’m going to let that decide.

Alexandra, do you look at it any differently?

: No. Patients make decisions based on a whole number of factors sometimes that we can't predict. The JAK inhibitors will be that kind of second-line systemic agent, but behind what and in what order is the question. Some patients making the decision weigh the efficacy and the safety that you're telling them about may reach for a biologic first, but there are other patients who don't like the idea of doing an injection and are motivated because they have a wedding in 2 weeks and need to have that quick clearance. We use their own personal set of circumstances or preferences and make the decision that feels best for them. There is going to be a role for their usage in a whole number of different orders like just when viewing that treatment algorithm. It'll be interesting to see what we do now 3 months after and what we do 3 years from now, and how that will evolve.

Raj, are there any special ways that you take this patient who could go on any one of them like a new topical JAK, new oral JAK, or biologic, and make that decision?

Yeah. I want people to get as clear as possible, to get their symptoms as controlled as possible, and to get them to be the best “them” that they can be. But one-sided treatment plans oftentimes are very difficult to follow through with in the real world. You have to work with your patient in terms of what's going to work for them and that is largely what is going to parse out how somebody falls in terms of a topical route versus a biologic route versus an oral route. There are subtleties along the way in terms of what might be practical for them and what other comorbidities and indications might be there, particularly in the case of biologic therapy, where we're starting to see some other indications for biologic therapy that overlap with people that have atopic dermatitis, and even in the case of oral JAK therapy, where there may be other indications that overlap with individuals that have atopic dermatitis. This is going to be a time argument where this is going to largely settle out, but at this point in time, the patient voice is going to have to be paramount to the decisions that we make.

Great. Thanks so much. This was a great overview on how to practically approach these new treatment options.

Experts in the management of atopic dermatitis assess the use of JAK inhibitors in clinical practice and considerations for treatment selection for patients with atopic dermatitis.

JAK Inhibitors in Clinical Practice for Atopic Dermatitis Treatment

Thus far with the JAKs, has your experience been positive? Do you feel like they're living up both orally and topically to what our expectations were? Where are they over-excelling? We talked a little bit about this. Ale, do you feel like you use them, and do you use them as monotherapy and feel that this is where they're most successful? Do you use them with steroids? Everything, especially the topicals, is studied as a monotherapy. They tell us that we shouldn't be using it with other agents. Are you doing that in real life? What's going on?

: For the systemic JAKs and for systemics in general, whether you tell patients to use or to not use topicals, often people will supplement, or since systemic JAK inhibitors are so fast-acting, oftentimes the topicals get dropped quite early if they are on board at the beginning. If you look at their concomitant topical steroid data, they barely got a boost because most patients are well controlled just with monotherapy use. I like to get a clean picture of what the drug is doing on its own. I usually say, we're going to start this new medication and let it behave on its own. The itch improvement happens so early that I don't think people are reaching to supplement with many of their topicals—for the majority of patients. The topical JAK inhibitor is somewhat different and patients are not always reaching for it if they're having an acute flare, but will for more maintenance or proactive maintenance. The majority of time it is being used as monotherapy or on some type of alternating basis with a low-to-medium potency topical steroid.

So you have no problem giving a patient both 2 potentially topical steroids? Raj, do you give patients more than 1 prescription?

: Yeah, sometimes you're forced to. It hurts me on the inside to contribute to polypharmacy, right? By definition, that’s anywhere from 2 to 11 prescription medications. When you think about it, as dermatologists we're committing that cardinal sin constantly because we can't go 1 visit without giving 3 to 4 things. I'm as big of a culprit as they come. The nice thing about these new therapies is that we're able to simplify the regimen. We always talk about this step-up additive approach; something we've been trying to talk about in addition is now a step-down simplification approach. If you're moving up to a higher step therapy, much like Ale said, even the data would reflect that you're not going to get that much of a boost from concurrent topical corticosteroid use in the case of oral JAK inhibitors. They can largely work on their own. Similarly, much as Eric very nicely put it, when you look at that phase 2 data comparing triamcinolone with topical ruxolitinib, it's really doing as if not more heavy lifting than that is. So you're probably not going to get really that much more additive benefit as well over something that's going to be maybe equally or even less potent. With many of these new medications, as we start to get familiar with them, I'm trying to work them in as monotherapy, but in the circumstances that require it, it’s OK to add on a normal topical antiinflammatory. Over the course of the next year or 2, this is when most of our real-world data and reports are going to start to come out of what does a real-world prescribing pattern look like? How are people combining these therapies? How are people not following the exact indication? It's going to give us a good idea if there are any safety or efficacy signals that we just weren't clear about before.

What has your experience been, now that these drugs are available, with blood monitoring? Are your patients pushing back? Do you feel like clinicians are pushing back, or do you feel like this is OK that we can do baseline labs? Do you have an established routine at this point in terms of what you feel is the appropriate blood monitoring? Ale, what do you do?

: I had that same question myself when I was counseling patients on the laboratory monitoring—just kind of a curiosity on how it would be received. In the context of a medication that you've gone through the label with a patient on, there's some comfort that patients get in your saying that there are these risks, but we are going to be doing laboratory monitoring with the exclusive goal to make sure that you're staying safe on this drug. I have not received any pushback on the laboratory monitoring. I am doing baseline labs and bringing patients back between that 4- and 6-week mark to check labs again. No one's past that second visit. But again, around week 12, we'll recheck the lipid parameters, per the label. Then, we'll do labs between every 3 and 4 months after that. Although, it's definitely still a work in progress for me. I welcome others’ input too.

I agree with you. Eric, do you have this down to a science? What are you doing?

: I do not. There are some subtle differences right in the package insert. For example, in upadacitinib, they say to check lipids at 3 months, which is recommended by the FDA [United States Food and Drug Administration], and then as needed thereafter, whereas axitinib does have a small percentage of patients who can reduce platelets at 4 weeks. That's less than 5% of patients. The recommendation is that you check a CBC [complete blood count] at 4 weeks after use. I'm going to have a consensus paper on how can we just make this simpler and not worry about all the individual details? If you wanted to not do that, I like the check at 4 weeks, redo the labs at 4 weeks, and redo them at 3 months for now, and if everything's normal, we're all going to have different frequencies. We need more real data, but after 3 months, if nothing is wrong, you could go every 3 months or maybe every 6 months potentially after that. I'm happy to hear from my colleagues because this is a new area that we're talking about.

It's interesting, because why is it not on the label to do a base? How many people walk in off the street and have abnormal panels at baseline? If you're doing a disservice, and if you don't know who the patient is when they came in, did they have a problem at baseline or not? Even though it doesn't specifically state it, that's kind of critical to do.

Raj, any other thoughts on this? This is one of the things that people are going to have the most questions about: Am I doing it right? When can I stop?

: Yeah. Some degree of hesitancy about the adoption of new therapy comes from the other stuff that you have to do aside from just prescribing...Let's hack it back to psoriasis for a second, and let's take it back to not that long ago: the days of sort of TNF [tumor necrosis factor] blockers, right? There are a lot of similar overlaps into some of the things that you're doing at initiation—some of the things you're looking at in follow-up. Many of those patterns just fell into place and became a commonplace, and people got comfortable with it. We are saying the same thing. You're going to check a little more often early, and later on, you're going to check a little less often. If you just want to break it down at the beginning, you're going to do a little bit of ruling out infectious stuff, and beyond that, it's going to be the kind of labs we're very used to. When you put it in a big picture like that, it's not that different from monitoring that we've become comfortable with whether it be conventional oral immunosuppressive agents or whether it be biologic therapies for other inflammatory diseases. I don't have too many differences in terms of what everyone here has nicely said they're going to do, but I do think taking a nice big picture view of it about what else we have done with inflammatory disease over the past 2 decades will maybe make people feel like this isn't some weird foreign thing. It's quite familiar to what we've done before.

We have so many great choices right now. If a patient comes in, and they're in that in-between category, where could we potentially use a good topical, a topical JAK, an oral JAK, or a biologic. What's going to make you decide and push you to 1 direction versus another? Eric, how do you decide?

: It's important for the clinicians to know that the indication has some wording in that and it makes it sound as if the indication is that if they're a systemic candidate and they were failed by at least 1 other systemic therapy, it's unclear whether they need to be failed by a biologic or any their systemic agents. As a clinician, you need to read that and then be comfortable with how you interpret that so you can defend that in your note, or if you are going to go straight to an oral JAK, for example, after a 1-week course of prednisone, and in your mind, that's trying another systemic. There might be some practice variation. But to answer your question, I'm going to see this as a potentially second-line systemic, and then it'll roll to the patient preference. There are other biologics available other than dupilumab, for example. Do you switch to a different biologic class? Do you go straight from a traditional immunosuppressant to a JAK inhibitor? It's going to be patient preference and their risk aversion, their comorbidities, and all that. I'm going to let them decide.

: No. Patients make decisions based on a whole number of factors sometimes that we can't predict. The JAK inhibitors will be that kind of second-line systemic agent, but behind what and in what order is the question. Some patients making the decision weigh the efficacy and the safety that you're telling them about may reach for a biologic first, but there are other patients who don't like the idea of doing an injection because they have a wedding in 2 weeks and need to be very clear and have that quick clearance, use their own personal set of circumstances or preferences and make the decision that feels best for them. There is going to be a role for their usage in a whole number of different orders like when viewing that treatment algorithm. It'll be interesting to see what we do now 3 months after and what we do 3 years from now and how that will evolve.

Raj, any special ways that you take this patient who could go on any 1 of them, a new topical JAK, new oral JAK, or biologic and make that decision.

: Yeah. I want people to get as clear as possible, get their symptoms as controlled as possible, and get them to be the best them that they can be. One-sided treatment plans oftentimes are just very difficult to follow through in the real world. You have to work with your patient in terms of what's going to work for them and that is largely what is going to parse out how somebody falls in terms of a topical route versus a biologic route versus an oral route. There are subtleties along the way in terms of what might be practical for them, what other comorbidities and indications might be there, particularly in the case of biologic therapy, where we're starting to see some other indications for biologic therapy that overlap with people that have atopic dermatitis and even the case with oral JAK therapy, and where there may be other indications that overlap with individuals that have atopic dermatitis. This is going to be a time argument where this is going to largely settle out, but at this point in time, the patient voice is going to have to be paramount to the decisions that we make.

Thanks so much. This was a great overview on how to practically approach these new treatment options.

Alexandra K. Golant, MD; Raj J. Chovatiya, MD, PhD; and Eric Simpson, MD, MCR, share their approach to prescribing decisions for oral and topical JAK inhibitors for patients with atopic dermatitis.

Eric Simpson, MD, MCR

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