Eric Simpson, MD, MCR

At this point, I want to move a little bit more towards talking specifically about JAK inhibitors and how these have revolutionized our treatment approach to atopic dermatitis. Raj, let's start with you. Can you give us some background? What are they? Talk a little bit about what makes them suitable for the treatment of atopic dermatitis.

 Sure. For a number of decades, we've been living in this revolution of biological therapies right across psoriasis and atopic dermatitis, so the thought of an oral small-molecule therapy requires a little bit of mental resetting. Let's just talk a little bit about high-level concepts of inflammation and immune signaling. You can largely think of it as 1 big relay race. The fancy word that we use is signal transduction, but let's talk about it like a relay race. You have signals hanging out on the outside of the cell. They're trying to tell the cell to do something on the inside, such as cause changes in transcription, translation, and signal inflammation, barrier changes, and all of that good stuff. You can think about biologics or antibodies acting on the outside of the cell. They're blocking a receptor. They're preventing something from binding to the receptor or stopping the signal at that point. This would be something that drags the specific cytokine like IL-4 [interleukin 4], IL-13, or something like that. Now, JAK [Jansen kinase] inhibitors actually act on the intracellular portion of the cell meaning that there's a family of proteins, JAKs. There are 4 of them: JAK 1, 2, 3, and TYK2 [trosine kinase 2]. They bind in varying combinations to different cytokine receptors on cells. When you get something binding on the outside of the cell that causes changes on the inside of the cell, JAKs activate a class of proteins called STATs [signal transducer and activator of transcriptions], and those go into the nucleus and do their thing. You could imagine that a small-molecule JAK inhibitor is not going to be an antibody, but rather, a small molecule that gets inside of the cell and that can work on some of these JAK proteins. One of the reasons why these are exciting for atopic dermatitis, as my colleagues keep talking about, is this heterogeneity of disease. We know that there are very different combinations of signs and symptoms and burden across individuals. A lot of that has to do with subtleties in how all of this signaling works. The cool thing about JAK inhibitors is a single molecule can work across multiple different signaling pathways, binding to 1 of these JAK proteins and thereby stopping inflammation at a very early source. Whereas a biologic therapy might be an injectable, you're going to take it through the bloodstream, absorb it that way, and an oral you take once a day. It's a molecule that makes its way through the cell, and it functions in a very different way.

That was a great overview. We're learning so much. One of the issues is when I think back to medical school and residence, I didn't learn about the JAK-STAT pathway, so we're having to start to learn our immunology a little bit better and over again. That was a nice overview of what we can expect and why they might work particularly in atopic dermatitis, as well as other inflammatory skin diseases.

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Raj J. Chovatiya, MD, PhD, provides an overview of JAK inhibitors and their use in atopic dermatitis treatment.

Role of JAK Inhibitors for Atopic Dermatitis Treatment

Ale, I want to turn to you. When a patient comes in, do you talk to them up-front about what their goals are, and how do you set those goals? Does it differ depending on the age of the patient?

Yeah. Goal setting is important, and asking patients what does ‘ideal’ look like for them? The answers are sometimes different. You can see a patient with full-body eczema who will just tell you, “If I could just get rid of my itch, I don't care how my skin looks.” Obviously, ideally, we'll target both, but you get a sense of what is driving their suffering. For most patients, my personal goal for them is to allow them to get to a point where they're living their life as if they don't have this chronic disease—like without their atopic dermatitis. I say, “This is going to be with you for your life, but it doesn't have to control your life or control the narrative of your life.” Like Eric was alluding to, if they're willing to use topicals, do they never want to see a tube appointment again? What would be their happy place in that mix? In terms of the age of the patient, I don't find that the goal-setting differs that much, although for younger patients, the goals are being set by our parents and caregivers. As Raj had mentioned, understanding how the disease is impacting the family unit is important—not just parents, but siblings and the whole family dynamic because it does trickle into every crevice of life. Getting a sense of how you can intervene and minimize the family's suffering is important too. That all plays into how aggressively and how quickly you escalate up-treatment ladders and things like this.

 Yeah. I agree with this whole conversation. In psoriasis, we have a target to treat. In atopic dermatitis, my goal generally is that if you ask somebody who has a moderate-to-severe disease, “How often do you think about your skin?” They look at you like you're a crazy person. Like, “I'm always thinking about my skin.” My goal is always to take it from right here and put it back here: “I don't live my life around my atopic dermatitis, but I am somebody who happens to have it,” so that is my goal is always. When I say, “How often do you think about your skin?” and they go, “Oh, right. You know? Yeah. Not so much.” Then I know we're really there. But Raj, I know that as physicians, we come up against a lot of challenges and certain limitations. Can you address what you think the common ones are and how you try to handle them?

Sure. What my colleagues have beautifully discussed is everything that goes behind shared decision-making, like this concept of working with the patient to try to address what's important to them and what's important to you and come to a happy medium. When I think about treatment choices for adolescents and adults, people largely are interested in any one of these things. A treatment that works, something that's going to work quickly, something that's going to keep working, something that they feel safe about, something that has improvement of their skin and their symptoms, something that they can actually get their hands on, and a category that we haven't paid enough attention to: something that's feasible, something that they're actually going to be able to do, and something they can actually afford and make it a part of their day-to-day plan. It's really important in the back of your mind to be thinking about those categories when you're talking about treatment options with your patients, and not everybody values the same ones nor do they have the response to the same ones. For somebody, they may want something that works quickly that may not matter to someone else. For someone, cost may be a big issue. That may not matter to someone else as well. That's the really individualized therapeutic plan that comes with working on trying to find the best plan forward for our patients with atopic dermatitis.

Eric talked about the difference between the systemics, the orals, and the topicals. Do you ask your patient upfront, “Do you want a topical or do you want an oral?” Because I know sometimes we'll go through a whole long decision-making process and we'll prescribe something systemic; and then you realize, no, they're not going to take anything systemic. They're just not going to go there. Do you address that up-front and try to weed that out?

 Yeah. I like to think of it kind of like that scene of the matrix, where you have 2 hands and you're like, red pill or blue pill? I like to make sure that they understand that we have choices and each of those choices has both strengths and negatives when it comes to the severity of their disease, both in terms of signs and symptoms and what they value. I never would've believed this when I started out training: you put it in the patient's hands, they largely start to lead you towards what they want to do as long as you give them the chance to add their opinion. That is very powerful. At the end of the day, me forcing someone to do a systemic therapy that I know that they're not going to follow through—it's not a good therapy because they're just not going to do it. I'd rather that they have a topical that they use well, even if they're not clear by my standards that I've set in my mind rather than something that they may intermittently use or just not come back and see me anymore.

That's interesting. I'm going to come back to you, Eric. When you're talking about the treatment choices, do you look at your patients and say, “I see you and I see your disease. This is what I recommend based on your severity, your age, and everything else.” Or do you provide them with a menu of options and let them choose? It's interesting because people approach this shared decision-making a little bit differently, so I'm kind of interested in each of your approaches. Do you say, “This is what I suggest? Or do you give them a menu?

 Raj went over that well. I'll just add a little bit to that. Patients approach that, maybe providers do, but also patients do. Some of my older patients want me to be more paternalistic and my younger patients do not. My older patients get disappointed in me because I keep trying to put the decision-making on them, and so sometimes you have to be paternalistic, but I prefer an equal kind of shared decision-making process. No, I don't necessarily choose for them, and I wouldn't give them options that I think are not appropriate given their medical condition or their severity. I try to tailor my choices for them based on my medical expertise. Then, if I feel like there are just fine choices with the slight trade-offs of safety and efficacy, I put that into their court and see. I can't remember who said it, but if you know their preferences early on in terms of risk aversion or other things, that just helps move the conversation forward and get to a spot where they can make an informed choice.

I agree with you. Ale, do you feel like there's a difference too, depending on the age of the patient? Some want, “You're the doctor, so you should tell me.” Others say, “You know what? Let me understand the whole menu—the whole situation—and let's figure this out together.”

I practice in Manhattan, where people sometimes come having done a lot of their own research and have strong opinions on treatment that they've read about. Patients know themselves the best, and I really stand by that. One thing that can be helpful in talking to patients—especially these individuals who have had atopic dermatitis since childhood and see you decades later into their disease journey—is labeling. There are topical patients and then systemic eligible patients, but the way that the [United States Food and Drug Administration] FDA labels these treatments, it's this moderate-to-severe category. For patients that fit into that bucket in my mind, I do think that there is some power in telling patients, “I view you as a moderate-to-severe patient, or in my opinion, you have pretty severe disease. I want you to know I'm taking this seriously, and let me tell you about treatments that did not exist 5 years ago. If you want your outcome to be different, we can get you there.” Many patients approach the conversation a little bit jaded because they were only given and cycled through topicals for so long. As much as I want to move away from these kind of very inorganic, mild, moderate to severe, I think there is some power in labeling patients and telling them, you are basically a topical patient or a systemic-eligible patient, and this is why.

I agree with you. For some of our patients who are on the borderline, we have some newer agents now, whereas I might not have thought that I could get them under control with the topical. This is a new world and now, we have to try again.

Alexandra K. Golant, MD; Raj. Chovatiya, MD, PhD; and Eric Simpson, MD, MCR, discuss goals of therapy for patients with atopic dermatitis and challenges physicians face in management of  the disease.

Treatment Goals and Challenges for Atopic Dermatitis Management

Let's go on and talk a little bit about treatment considerations for the management of atopic dermatitis. Our treatment approach to atopic dermatitis has evolved over time. Overall, we need a 2-pronged approach. We need to be able to get those flares under control, but we also have to have a long-term game plan. Eric, can you talk to us about where we've come from? What are our traditional treatment options?

 I'll break it up into topical and systemic. In the topical space, over the years and through the IEC [International Eczema Council] guidelines and expert consensus recommendations, you approach a patient as a topical patient, and if they fail topical therapy or good regimen, then that identifies someone as needing systemic therapy. I tell my patients like that. Sometimes I've asked them, “Do you see yourself as someone who may be able to get control with topical therapy? Or do you think that you need something more than that?” I'm always surprised, and you get a sense of what they're interested in. Patients say, “No, I think I can do this topically,” or “No, it's not working for me over the last 20 years. Tell me what else is out there.” In the conventional treatments for topicals, topical steroids are the workhorse, but we're learning that it sometimes leads to adverse effects, especially with more moderate-to-severe diseases and depending on where you put the therapy, but topical steroids are cheap and they're highly effective. They just need to be carefully monitored and instruct to your patients to not overuse it and that's sometimes challenging. Then, we have a nice array of nonsteroidal treatments like the topical calcineurin inhibitors. We'll be talking about a new topical JAK inhibitor, as well as the topical phosphatase inhibitors such as crisaborole. We have some nice nonsteroidal that allows you to be an artist in terms of individualizing a plan for your patients on the topical side. Now, on the systemic side, the traditional treatments have been the traditional immunosuppressants that are not FDA [United States Food and Drug Administration]-approved for atopic dermatitis, but they have given us a way to treat patients before we had FDA-approved therapies. So, they still have a place. They're cheaper than the new therapies and some of them work quickly, like cyclosporine, and can be highly effective, but are not great long-term options. The drug survival for a lot of these traditional immunosuppressants are not that good, but they still play a role. I still prescribe them, but I'm prescribing them less and less as the new targeted therapy starts coming up.

Yeah, that's great. We've had a lot of options in the past and we have a lot of newer options that we'll talk about subsequently.

Eric Simpson, MD, MCR, reviews conventional topical and systemic therapy treatment options for the management of atopic dermatitis.

Conventional Treatment Options for Atopic Dermatitis

When the patient comes into the office, I want to give each of you a little bit of a tip: It can be daunting. You have a new atopic patient coming in. Can you just give us a tip about how that initial consultation goes? How long does it normally take? What do you do to establish that relationship and set appropriate expectations? Eric, do you have some tips for a busy practitioner when a new atopic patient comes in?

 Yeah. They're not going to financially like this tip, but my first tip is at least a 30-minute consultation. I'm in the university setting, so we can do that, but it usually takes longer than that. A little time investment early on will make it easier and more efficient later on. Just invest in that first visit primarily. I try to do 2 things. The first thing is that I want to confirm the diagnosis and to make sure mentally that I've gone through the steps and that I'm not anchoring. I want to just go through it even if it's obvious to make sure that they don't have CTCL [cutaneous T-cell lymphoma] or allergic contact dermatitis. Once I have the diagnosis right, then I want to see where the patient's understanding is—like if they're coming in with this agenda of, I want a cure. I need to know that. Usually, there's a tip. If they've seen 4 other dermatologists or they haven't been told that there's no cure for this. That's a really tough step. You have to build that rapport and let them understand that. Sometimes, it's challenging, or they've never been told that before. Once I understand where they're coming from and what their understanding of the disease is, then we can work from there together on coming up with a treatment plan, but that's my general approach.

I agree with you. You have got to establish that trust and that relationship and let them know that we each have our part to do. You do your part as the patient; I'll do my part, but it really is a team approach. Ally, any other suggestions for a busy practitioner?

 Yeah. Similar to Eric, I also practice in an academic setting, but the first visit, which I always call the “disease state”: sometimes disease state reeducation, particularly for patients that have had this disease for many decades, and bring them up to speed about how we view atopic dermatitis now as a systemic chronic inflammatory skin disease. That understanding and that acceptance, particularly for our systemic-eligible or our moderate-to-severe patients, makes a big difference because it helps them to understand why this visit's going to be different. We're not going to just talk about creams and ointments; we're going to talk about systemic treatments that we need to get you clear. The only other thing that I'd add on to that is goal setting and understanding what the patient's goals for their treatment are. Are you OK with having to use a topical sparingly? Do you want to be clear? Do you want to be completely free of it? Where is your goal, and how we can partner together to get you closer to that goal? How is it different than where I'm seeing you right now? Those are things that have been helpful to me, but the visits are lengthy. I completely agree with that.

Raj, do you provide your patients with resources or handouts, or send them to the Internet? How do you end that visit or make sure that they have the information that they need?

Sure. They could go Googling and find anything and everything about what you're going to talk about. Much like my colleagues have said, getting the information that you want in that first visit is key. There are a lot of good sources of reliable information out there. I like to review some of that with them. There are great resources through the National Eczema Association, the American Academy of Dermatology, and things that have been vetted by a variety of experts, patients, and caregivers themselves that I know and trust. I have my own handouts that I make for my patients. Something that providers can do ahead of time is to just come up with the bare bones, or to even fill that version of what you think the eczema action plan should be for your patients so you don't have to be writing this from scratch every time. Largely, there should be some editable areas for the things that you're going to be doing, but that's going to be the backbone of what you're talking about every time that they come back. The 1 thing that I tell my residents is that if you feel like you're repeating yourself at subsequent visits, you're doing a good job because this is a chronic condition. A lot of it just requires coaching and keeping up the spirits of dealing with the normal flares and remissions that come along the disease course.

I agree with you. You can say it, say it again, and say it at every visit. Hopefully, at 1 point, they’ll actually hear you.

Drs Eric Simpson, Alexandra K. Golant, and Raj J. Chovatiya share their approaches to atopic dermatitis care.

Eric Simpson, MD, MCR

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