Peter A. Lio, MD

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: So great question about reevaluating formulary and how formulary decisions are made. Obviously, this all depends on or is driven by the type of plan you’re actually maintaining. So if you have a Medicaid plan, then you’re essentially at the mercy of how the Medicaid plan covers that product. You can’t go and create your own formulary pathway when Medicaid has a different pathway. That’s completely driven by a PDL [preferred drug list]. And we know that’s also tied to rebates and how the competitors have positioned their rebates to Medicaid. Then, in regards to commercial options and some of the other formularies are obviously a little bit different. With commercial options there is obviously more of a PDM [proportional disease magnitude] driven formulary guidance in terms of how a product is positioned more favorably from a PDM perspective. There’s a lot that is driven there. And then, of course, there are clinical studies that go into driving the formulary, too.I think reevaluation usually happens when let’s say, a new drug comes out and we haven’t reviewed it, and we’re receiving probably 20 or 30 requests a month. I think we need to establish guidance in terms of how this could be utilized, so we can actually guide our providers and maintain or preserve our formulary status. I think that kind of drives that. If a manufacturer approaches us and says, “Hey, we wanted to see if we can have a value-based contract,” or some type of contract where they have identified that they wanted to have a more favorable preference of their product on the formulary, then of course that will also trigger the need for reevaluation and how a product is positioned in the formulary. Then, as new agents come through the market, we have them reviewed because we’re going to be getting requests. But if we’re getting 1 or 2 requests a month, it’s not going to trigger an evaluation of the formulary. Then of course, if entities like Medicaid are determining or pushing out their formulary recommendations, that will also trigger us to reevaluate our formulary. At the same time, we’re looking at what are our needs while looking at our commercial options, and our Medicare options. I think not just doing a one-sided approach where we’re just looking at that Medicaid reevaluation, but we would do it, whole class, with all of the lines of businesses.

How do you actually create access for effective treatments? It’s really through innovative contracting or, I think, the bottom line to any payer is that they’re trying to have a more favorable cost profile so that they can sustain their PMPM [per member, per month], and also treat the number of patients that they have. So it’s thinking through what is the volume of patients that this payer is going to have to treat? And can they do that while preserving the PMPM? And what kind of partnership looks like with that payer to help them through that? I think we kind of saw this as a prime example in hepatitis D, where nobody anticipated the volume of patients that you would have, and then the cost that was built into the system, it was just not sustainable for payers. Even though the most effective treatments that we’ve ever had in that disease, curable treatment, an 8 to 12-week course, and there was significant access to it because of the way it was positioned from a cost perspective. I think really working with payers in understanding what that price-setting should look like, based on the volume, so you can actually have that access for those patients.

There are groups such as the National Eczema Association, of which I’m a proud board member and scientific advisory committee member, and they do try their best to advocate for patients. They have resources available to patients. As I said, I do work with a number of companies that have programs for patients. And I’m a big proponent of them. I wish we didn’t need them. It’s one of those crummy worlds that we have to fill out paperwork to have a company help a patient. The whole thing is so silly, but that’s the reality. These programs can be amazingly effective in getting patient assistance. Not only for getting a drug that they can’t get, but also helping with copay. Some of the medicines have high copay and the companies will reimburse the patient thousands and thousands of dollars of savings, which is real money for many families, for any family. I don’t know anybody who could pay for these things out-of-pocket. And if they could, then hopefully they’re doing charitable work because then you have a lot of capital, then you can use that money for good things. So those are some of the things we can do. We can try to work together to find specialty pharmacies, a huge part of my day, as dumb as it sounds, is shopping around; This pharmacy mail order can do it a little cheaper than that one. It seems like again, healthcare utilization, there’s a shortage of dermatologists. People get so frustrated that they have to wait so long to see us. What am I doing? That’s part of what I’m doing. I’m trying to find a cheaper pharmacy for people. So these are things that I wish we could alleviate. I wish there were better techniques. Again, the payers really are in the driver’s seat. They could make everybody’s life a lot better. I wouldn’t mind it being a little stricter; Here’s our criteria, but it’s clean, simple, and universal. That’s why I think you’ll hear some doctors, not all, I don’t want to put words in anybody’s mouth, but they’ll push and I’m in the group. I would totally consider a single-payer healthcare system. I stand to lose a lot, money-wise. Presumably, I’d get paid a lot less. Why? Because of the stress and the ridiculousness and the shenanigans, it’s worth something to me. I’d be willing to pay it from my salary to have simplicity. And that’s saying something.

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Current strategies used to evaluate the performance of therapies used to treat atopic dermatitis and guide formulary decisions, and recommendations to help patients receive access to effective therapies.

Increasing Access to Effective Therapies for Atopic Dermatitis

: In regards to the question about the difficulties in managing this disease, I think a lot of it stems from patients not having access to appropriate providers who actually have expertise in this. Then, the second aspect is that in some of the economic analyses that were done, we did see that patients of African-American or minority descent actually had poorer outcomes and lower satisfaction compared to the predominantly white patient population with atopic dermatitis. It shows that there is a disparity in access to care, education, and the connection with the right providers. I think that really drives some of the other indirect costs that we’re seeing. I think we talked about what happens to a patient with ineffective therapies, or not having the appropriate diagnosis. And I think being a managed care Medicaid health plan we do see a lot of those disparities in these patients. So I think there’s definitely more that we can do, and it’s definitely challenging when you don’t have resources poured toward creating that open forum for patients to be able to access despite having all of these disparities.

I think the landscape is definitely changing rapidly for atopic dermatitis. And you’re absolutely right in terms of not having the appropriate expertise. If you look at when I am part of the direct care of patient responsibilities, many providers are actually very used to how they manage a disease. So when a new drug comes out, there’s always some skepticism about adopting new therapies right away, even if they may be highly effective. And then, of course, not having a specialist who’s prescribing this, who may be well versed in the new agents that are coming into the market, and how they should be utilized. But where does it really fit into the treatment for many of their patients? There was a survey done by Bryan Chang and his team—he was a senior author—that was presented at the atopic dermatitis virtual symposium recently, I believe. Essentially, they identified thousands of patients who had atopic dermatitis and they did a 5-question patient satisfaction survey, using the CAHPS [Consumer Assessment of Healthcare Providers and Systems] methodology, which hospitals use HCAHPS [Hospital Consumer Assessment of Healthcare Providers and Systems], so it’s actually measuring the providers. Did your provider explain to you the disease that you have in detail? Were you satisfied with the agent that they prescribed for you in your disease? Were they timely in providing you with information such as your labs and follow-ups and things like that? It was interesting because it was a 5-part, 5-question assessment, where many patients indicated they were not satisfied with their provider’s support. Essentially, there was also a finding that their disease wasn’t as controlled. So disease control was directly tied to patient satisfaction. So it’s really interesting when you can actually understand the dynamics of treatments and the treatment of the disease, where patients are probably not seeing the right providers and not getting the appropriate treatment in a timely fashion. There are a lot of barriers, I think, in optimizing these treatments, because maybe lack of provider expertise and not understanding the pipeline agents.

: There are a lot of barriers to access, and this includes everything from misinformation to disinformation. Sometimes people come in and say, “I heard topical steroids are super dangerous. I don’t want to even touch them.” That’s an important thing. It’s difficult to convince somebody to change his or her mind in 15 minutes. Talk to anybody who’s discussing vaccination status or political things. We’re in a time now where people have very strong opinions and are very confident about them. Sometimes I find that it’s easier just to work with people at that moment rather than try to push back all the time. We have to sometimes take what we got and work overtime to establish a rapport and relationship. Education is part of the barrier but the other part, of course, is accessing them in terms of costs.There is a very confusing thing in American medicine. Sometimes the super expensive branded prescription will be much more accessible for the patient than what would appear to be the far cheaper generic. And it can have to do with things like a manufacturer’s coupon or a program where the company says, “You know what? We’ll take care of it for a year.” And that is confusing and difficult. There’s a lot of push back on us saying, “Hey, stewardship, we have to save the system money.” When you really pick that apart, yes, I’m trying not to bankrupt our healthcare system, but as we’ve already said, it is a for-profit healthcare system. And most of the people I’m dealing with are private insurance companies. On the other hand, I also have to take care of my patient. That’s my first concern. I can’t change that unwaveringly. The first real piece that I have to focus on is the patient. So if they can’t afford the medicine, well, what are we doing here? Then I’m completely powerless. I am more than happy to utilize programs from companies that are going to help make it more accessible. And sometimes it’s a better product to boot. It’s really hard. You’re making a sacrifice sometimes to pick a generic medicine, which you know less about. Sometimes it’s a different formulation. They are often the cheapest ingredients and I’m happy to do it. But when the price of the patient is $300, you’re saying, wait a minute, you can get the branded one that we know is nice. You can get that for $10. This is silly. These are some of the things that we face. Another issue is time. Patients have to do a lot in dermatology. If it’s just a pill, even that’s hard to get people sometimes to take, but when it’s a topical routine, it does take a lot of time and energy. So that could be another barrier to care. And we often just say, just put this cream on, but it’s not that easy. That is another aspect that we really have to consider for our patients and their families

: I think one of the biggest challenges that patients will face is going to be the cost-sharing involved with many of these agents. And as a payer, we have to basically use the dictated formulary that is chosen by the employer groups. Essentially, I think there’s going to be higher scrutiny for the oral agents, but less scrutiny for the topical JAK [Janus kinase] inhibitor. And I think Medicare patients will definitely be impacted more just because it is hitting part D for many of these patients.I think with oral agents there are always adherence issues. I think that’s one of the drug interactions and the system toxicities. And patients, in this specific disease, are not used to having drugs like a JAK inhibitor. I think just knowing some of the side effects, or listening to the side effects, patients may actually abandon therapy. I definitely think that there’s a lot that will need to be done in making sure patients stay on therapy. But in terms of formulary positioning, I think that’s going to be really driven by a lot of the cost factors, and even if there are opportunities for value-based contracting, or risk-based contracting, that may actually—can actually put these agents more frontline. I think there are definitely differences in how that will play out once they’re approved. Some are already being approved so I think we have some visibility on the cost. I think the cost will be one of the biggest factors where there will be a placed formulary in tiers in terms of the pathway and going from topical to oral.

Payer and clinician insight regarding access to effective therapies for atopic dermatitis and potential challenges adopting new therapies, including topical JAK inhibitors, into clinical practice.

Barriers to Treatment Access in Atopic Dermatitis

: There are still a ton of unmet needs for atopic dermatitis. I think one of the biggest areas right now and a big focus is a primary prevention. We would love to figure out how to prevent this disease and right behind that is what do we do for our littlest ones?The babies, as we've talked about, we don’t have many things approved down to this range. We’re excited to see crisaborole, get down to the 3-month range, but I even have 6-week-old babies. These are really tough so we would love for some more research and insight into how we can help these babies the best with best practices. And is there a chance that we could actually prevent or alter the course and modify the disease course of this by treating it appropriately early on? Maybe there’s some work going on in that? For other patients, I think we still need a lot more in the ICH [International Conference on Harmonization] domain. We still need to understand the microbiome. We need to be able to modulate that better. I’m very bullish that fixing the microbiome may be a real pathway, like an independent, powerful pathway to help this disease. I’ve seen some experiences already where it seems the microbiome was playing a very powerful role in all of this. I’d love to see more work done on sleep. I would love to see even more advanced things on skin barrier healing because right now if you notice everything we talked about pretty much focuses on inflammation. So it’s sort of every other area I think is still underserved relatively speaking, besides the inflammation/itch part.

: There’s a lot of unmet need in atopic dermatitis. I think we don’t have a lot of data on the economic burden—on both patients and the healthcare system. So I think there needs to be more data, especially with new agents coming to market. I think that we definitely can provide more insight into the benefit that these agents are providing for the healthcare system and the patients. Because there’s a quality-of-life improvement that’s going to be directly tied to healthcare resource realization. These patients are not with a life-threatening disease, but there is an impact on disability claims. There’s an impact on healthcare resource realization due to symptoms and productivity loss. I think there needs to be more data that kind of provides even payers, in terms of knowledge of assurance that these agents are actually doing better than some of the previous agents that we have in the market. And then I think the other unmet need is that we need to have identification of biomarkers to really help manage the clinical management of atopic dermatitis in different stages of the disease. So I think it…really making it personalized. I think that’s another unmet need because when you have so many agents in the market, which one are you going to be using? There needs to be more of a targeted approach or more of a pathway-driven approach, in terms of indications, comorbidities, and severity. And then biomarkers would kind of incorporate it all to be this predictive model of which patients are going to do better.That would definitely change the perspective on how we manage patients with all the different stages of atopic dermatitis.

An overview of limitations faced by payers and clinicians who play a role in the management of atopic dermatitis.

Unmet Needs in the Treatment of Atopic Dermatitis

: Numerous JAK inhibitors are coming to the market. Three of them are oral and then one is topical, which is ruxolitinib, It’s really interesting because from a topical perspective, you avoid the systemic adverse effects that patients may have. Then based on the literature that I’ve seen with ruxolitinib topical, there is a significant reduction in itching very quickly, within 12 hours of using it, and then that’s sustained for over 4 weeks. Some may even say that there’s a benefit that’s equivalent to a biological. That reduction in itch that is within 12 hours from a topical perspective, which avoids the systemic adverse effects, I think, is very appealing.

I do think that the cost of a biologic is going to be way higher always compared to the cost of a topical. Especially seeing some of the preliminary results, and having those benefits, [use of the topical agent] would definitely move higher in the utilization criteria. Maybe even failing the topical before the patient goes to a biologic, or requiring them to fail the ruxolitinib topical before they go to a biologic. Of course, we know that ruxolitinib cream is not going to treat those patients with asthma, who require an agent like Dupixent, or allergic rhinitis, or nasal polyps.I think having some of those comorbidities may push a patient to get a biologic over ruxolitinib topical cream. But I think there’s definitely a bigger pool of patients who would qualify for the therapy. Talking about the adverse effect profile of oral JAK inhibitors, this is not the case with atopic dermatitis, but recently we’ve seen a communication from the FDA that agents such as baricitinib and upadacitinib and Xeljanz all carry this warning from the FDA for an increase in blood clots and other adverse effects, such as cardiovascular events. This was seen in other indications like rheumatoid arthritis [RA] but essentially carried over to indications like GI [gastrointestinal] as well.

I think there may be hesitation from providers to reach for a JAK inhibitor over a cream, especially because of the FDA warnings that have come out recently, which changed the label of these, specifically with Xeljanz and baricitinib, that patients should fail a biologic therapy such as an anti-TNF [tumor necrosis factor] before they should be considered for JAK inhibitors. Obviously, they haven’t said that it applies to other indications besides RA and IBD [inflammatory bowel disease], where Xeljanz is used. I think that having those types of warnings would definitely be a consideration.

But the other thing I should mention is that we also have identified that the JAK inhibitors provide benefit in patients with alopecia concurrently with atopic dermatitis. That’s a huge impact on patients across various comorbidities. I think patients would also prefer having multiple benefits even though the provider is going to be reaching for the cream first.

I should mention one other thing as COVID-19 is still around; it hasn’t gone away. But baricitinib is approved through an EUA [emergency use authorization] for patients with [COVID-19–related] ARDS [acute respiratory distress syndrome] pneumonia. There is this other aspect that providers may be thinking about. Say they have a patient who is highly immunosuppressed and if they’ve been vaccinated but are still not sure about the amount of antibody protection they may have, having a JAK inhibitor, which is approved through an EUA for COVID-19–related ARDS pneumonia, if this patient develops COVID-19 and ends up having that overactive cytokine release syndrome, there may be a benefit for these patients. There are so many ways to spin this, but I think we would definitely prefer the cream over the oral agents, based on the cost, too, primarily, and the efficacy.

Right now, because the topical JAK inhibitor is so expensive, it is orders of magnitude more expensive than the things we have on the market right now. I’m reserving it for those patients really who have in earnest tried and failed at least topical steroids, probably one of the calcineurin inhibitors, and potentially, it’s not always appropriate, but crisaborole. The thing is crisaborole, as we said, it has its own niche, and for many, especially a severe patient, it’s not an appropriate thing to try. But for those patients who still need it, I’m really excited about it. There’s no doubt that for some of the patients, this could potentially mean the difference between having to go on a systemic agent and not, if we can get them under better control. So that’s exciting.

For the oral ones, I think for my personal practice right now, they’re going to generally be reserved for severe patients. They’re not something I think I will dabble in unless they really need it. Ideally, they will have failed something like a biologic first for my practice, because I feel that the biologics, in general, seem to have a more favorable safety and efficacy balance, at least the way it’s written. Again, that’s the hard part because the black box warning is so severe sounding, even if the truth is not quite to that level, it does make our life a little bit harder with talking to a patient.

They are probably going to be initially for patients who’ve had failures, who’ve done these other things, but if they prove themselves and as we get some experience, maybe we’ll start to say, you know what, they’re easier to use. It’s a pill; it’s not a shot. And maybe as I alluded to, we will be able to use them in smaller bursts for patients sometimes to be a true steroid-sparing agent. I’m excited about all of these options because we just have so many unmet needs.

Drs Shah and Lio explore where topical ruxolitinib fits into therapeutic sequencing in atopic dermatitis, compared with oral JAK inhibitors.

JAK Inhibitor Treatment Selection for Atopic Dermatitis

: We know that the inflammatory cascade that we talk about has several little checkpoints, and the way it would go is, between cells they might use a cytokine. So one cell releases a cytokine, let’s take IL-4 [interleukin-4] for example, it comes from one cell and goes across to another cell. On the surface of that cell, there’s a receptor, and that cytokine binds to the receptor. When the receptor binds, it undergoes conformational changes, and those changes actually transmit the fact that it’s been bound through the cell membrane. Because this is outside the cell and there’s the membrane inside the cell, it transmits it. And down inside the cell, there are these little enzymes, they used to be called just another kinase, JAK. Now they’ve kind of “backronymed” them Janus kinase. These guys can dimerize, and then they activate something called STAT [signal transducer and activator of transcription]. STAT is another little enzyme buddy that goes into the nucleus and then changes gene transcription.

The JAK inhibitors, therefore, play an important role in a lot of this inflammatory itch and a lot of cell regulatory aspects. By blocking this, these little molecules, these JAK inhibitors go into the cell, and they can interfere with this dimerization and activation of them, which is really cool. That’s a great thing because they should help with itch, inflammation, and overall disease severity. The negative when we play with the JAK system is that that’s not the only thing it does. It’s not just playing a role in itch in atopic dermatitis. It plays a role in, for example, making new red blood cells, white blood cells, and platelets. You can interfere with other systems sometimes, and that’s the question. A lot of the JAK inhibitors that are now being studied, and the one that’s approved, are relatively selective. We’re trying to target more important ones, but we know this is a relative term. If you use enough of them at a high enough dose, you begin to get some untoward effects. Those adverse effects can be serious for the oral or systemic versions because they already do exist for other diseases.

We actually have a history with these medicines, for example, in rheumatoid arthritis. We know they can cause increased infections because they’re lowering the immune system. There’s an increased risk of cancers or malignancies in the longer term. They also can cause issues with platelets and other blood counts because, again, they’re kind of tinkering with some of these things. We’re trying to find the perfect balance there, and for the right patient, I think they’re going to be transformative, but we want to be very sagacious about how we pick those patients and how we use these medicines.

The JAK inhibitors are really unique because there are a couple of aspects to this class of medicines that’s exciting. First of all, because it’s a small molecule, it can be prepared as an oral therapy, the pills, but also as a topical because it can penetrate very well. It gets into the cells and gets deep, deep, deep into the root of this problem. It can block this JAK activation, which is really important. The second thing is that they work extremely quickly; as a class of medications they work so quickly that it’s pretty astounding. Many of the things we talk about, for example, the conventional immunosuppressants that we might use, like methotrexate off-label, of course, it’s not approved for atopic dermatitis use in the United States—that could take months. Whereas these JAK inhibitors are on the order of hours to days, it’s amazing. What’s also nice is that because they’re a small molecule, they can come in and out of the body very quickly. So we’ve been long thinking, is this something we could use more intermittently? Could you have somebody start it, get much better, and then maybe come off for a while? That we don’t know, but I love the idea that it’s fast on, fast off, and we really can be in and out quickly as opposed to these slower agents.

The other thing about them that’s really exciting is that they come in different types and different dosages. It is also possible that we could be a little more artistic with them. We could use a very strong one to start and then maybe taper down the dosing or the schedule, or maybe even the drug, use a milder one for maintenance. All of this is still so cutting edge, I don’t know, but these are the kinds of things that make them unique and exciting as a class.

abrocitinib, and upadacitinib, from 3 different companies, those are the oral agents. Then the topical agent we have, just released, is called ruxolitinib. These are their drug names; they all have trade names as well. They are all similar in that they’re the same class. They all fundamentally have the same mechanism of action. But personally, as a clinician, I think it’s a little unfair to lump them completely together because each one is its own drug, even among the 3 oral ones. They have a little different binding selectivity. They have a little different dosing setup. It’s really fascinating. The oral ones, we think, will all be dosed twice daily. Maybe once daily, but it really seems like the plan was for twice daily. The topical one is also a twice daily cream.

All of them are going to probably have the same black box warning, for better or for worse. I was going to say, unfortunately, but I suppose there is a counterargument that we want to be as transparent as possible and educate as well as we can. The hard part as a clinician is that when we ratchet it up to a black box warning, there’s sort of no room for nuance. It’s one of those difficult situations because the patient looks at this and says, “Well, is this as dangerous as me smoking a pack of cigarettes,” which we also have a black box warning on. Is this the same level? The answer is, I don’t know, because we’re not having any gradations and because we’re not using our resources to help us know for a given patient. It becomes a very difficult conversation to have, especially for the topical cream, where it’s literally stated in the warning. All the warnings are about the oral formulations, so it is a very confusing thing to talk to a patient about who is now worried and say, “Well, if you read it, they’re actually not saying this drug at all, they’re talking about a different drug orally.”

This makes our job extremely difficult. It would be like if every time you got into a car, people gave you drag racing danger and precaution warning stuff. You’d say, “Well, I’m just going to work, I’m not drag racing.” Well, you’re in a car and people drag race cars, and it’s extremely dangerous, and you can be decapitated. And it’s like OK, I guess; at some point though are we doing more harm than good? That’s not for me to decide here, that’s for us as a society to come together, and our friends at the FDA to think about clearly if we’re doing more harm than good. The other problem is of course, if we cry wolf a lot, then we don’t have the ability to warn people when there really is something [to warn them about], because we keep escalating.

That being said, the oral medicines will certainly require blood monitoring and initial laboratory tests. We want to check liver, kidneys, blood counts. And probably every month or every few months, we’ll have to keep an eye on things, especially in the beginning. I sense that once things are better, probably we will not have to check as frequently. With the topical version, I don’t expect to have to do any blood work or plan to because as long as we’re using it appropriately and not on a large enough body surface area, which admittedly if you put a lot on, you could absorb it and then have the defacto systemic medicine, that’s real. But if we’re using it appropriately, I’d like to think that we won’t have to do that, and the safety issue should be much smaller. But there’s a lot to unpack there, everything from cardiovascular risks to blood clots, to cancer and malignancy, and also even things like infections or this acne-like eruption that’s been described. We have our work cut out for us.

Dr Lio discusses features that make JAK inhibitors, including ruxolitinib, abrocitinib, baricitinib, and upadacitinib, attractive in the management of atopic dermatitis.

JAK Inhibitors for Atopic Dermatitis

 For mild to moderate disease, we’re seeing some new innovations. The newest thing, which came out in 2016, was crisaborole. That was our first new, big treatment in 10 or 15 years. That was exciting and designed for mild to moderate disease. That’s still on the market and just got an indication down to three months of age, which is also exciting because a lot of the things cap out at two years of age and some things are for adults only. This is cool to have something for the baby range.

There’s a bunch of things being studied. There are other phosphodiesterase 4 inhibitors. There’s a new type of medicine that’s never been put out before, called tapinarof. That’s an aril hydrocarbon receptor modulator. I’m not sure if that will be for moderate to severe or for mild to moderate. There are all sorts of new barrier creams and moisturizers. There are a lot of new things on the market and there’s a whole bunch of work on the microbiome. I put all these things in this mild to moderate group because they’re relatively safe and accessible.

The second part will be, what about the moderate to severe? Those are the patients who are suffering the most. There we also have some exciting stuff. But with more power comes more responsibility, and the sword cuts both ways. We have some very powerful treatments like the oral JAK inhibitors, which are super exciting. They’ve been held up by the FDA, but I do expect all of them to get approval at some point. Those are extremely powerful and will help some of our most severe patients, which we have seen in studies.

We also have a new topical JAK inhibitor that just got approved a few weeks ago: topical ruxolitinib. That’s exciting for moderate to severe patients, and smaller body surface areas can be really powerful. There are also some new biologic agents. Dupilumab was our first biologic. It came out for adults only in March 2017 in the United States. Now it has been approved down to six 6 years of age, which is exciting. There are even data down to six 6 months of age. We’ll see if that approval happens. We’re excited, but there are other biologics, such as tralokinumab, lebrikizumab, and nimotuzumab. There are a bunch of things coming down the line. It’s an incredibly exciting time for even our most severe patients having nonsteroidal options too because many patients have burned out with topical and systemic steroids, and appropriately so. We don’t want to keep throwing steroids at these patients because they can cause a host of issues.

In broad strokes, generally we want to pick things that are less risky, have fewer side effects, and have fewer issues than the disease we’re treating. For these mild or moderate patients, we’re trying to start with more gentle things that have lower profiles of risk. There are a couple of things we understand. Moisturizers—usually over-the-counter ones, but these prescription devices are also as a device category—have been shown to help atopic dermatitis probably of all severities, but they’ve largely been studied in mild to moderate groups. They’re incredibly affordable for most patients. They’re very accessible in general, and their side-effect profiles are mild to minimal when we think about this.

The research and the barrier have come a long way with understanding about ceramides, specialized fats in the skin, and even more exotic things like finding ways to induce natural moisturizing factor, which helps with the acid mantle and pH control. Even some of the newest ones can directly affect the microbiome. We have some topical probiotic products. We have some products that contain enzymes that can actually kill Staphylococcus aureus

 We have hypochlorous acid and diluted bleach-type preparations as well.

We also have some new anti-itch products. Some are old ones that have been repackaged. Some of the larger over-the-counter brands have used things like pramoxine again. This can be very helpful for soothing itch and pain because technically pramoxine is an anesthetic, so it helps with both itch and pain for these patients. Then there are even some newer things being developed. In general, for these mild to moderate patients, we want to keep the risks to treatments very low and the benefits modest or better. They can help with our PDE4 inhibitors, for example; they’re very safe. They don’t have a black box warning, but they often sting and burn. That’s a problem. Especially in a kid, if they have an open sore and we put this on and it stings and burns, not only might it ruin it for that medicine, but they’re also saying, “I don’t want that medicine.” Sometimes it can be generalized, and they’ll say, “I don’t want any medicine. Don’t put anything on me.” We’ve seen this happen where they get a phobia of any treatment. That can make life very difficult. Even though the side effects tend to be mild, we want to be mindful of them and careful because we don’t want to burn those bridges.

An overview of topical and oral therapies used to treat mild-to-moderate atopic dermatitis.