Keeping It Simple: A Review of Topical and Systemic Treatments for Patients With Atopic Dermatitis

This transcript has been edited for clarity.

Steven R. Feldman, MD, PhD: Hi. I'm Dr Steve Feldman, professor of dermatology at the Wake Forest University School of Medicine in Winston-Salem, North Carolina.

Peter Lio, MD: And I'm Dr Peter Lio. I'm a clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

Feldman: We're talking about atopic dermatitis. Peter, I like to think of atopic dermatitis in two buckets: a mild bucket where we use topicals, and a more extensive bucket where I've got to use systemic treatment. Let's talk about topicals first.

The guidelines are incredibly complicated. I don't think patients are going to follow them. I like to keep the treatment simple. How do you manage it?

Lio: I think you're right. And it's actually getting more complex as we get all of these new agents. I like to break it down into two phases. I like to have a rescue plan when things are flaring up. Usually, that's going to be a topical corticosteroid — mid-potency, sometimes even a little bit higher.

And then I like to have a "when better" maintenance plan: something ideally nonsteroidal, in some cases a lower-potency steroid that can be used to either maintain and prevent flare-ups, or for those patients who have really severe disease, in a proactive way, they could be doing a treatment two or three times per week to those hotspots so that we hopefully will avoid needing to use those steroids. How do you think about it, Steve?

Feldman: I think that's ideal, but I'm jaded. My research on how poorly patients use their medicines makes me think, I'll just give them some triamcinolone. They'll use it till they clear up. And then when they need it again, they'll use it a little more.

Lio: I like that. And there is something to be said for keeping it simple. We know that some people can intermittently safely use a medicine or two and not have to go further.

But I run into two big hurdles. The first hurdle, and the one that is most common, is that patients say, listen, when I use the medicine, I'm better. But as soon as I try to take a break — and you told me, don't use it all the time, I'm not supposed to put triamcinolone on my body every day — things go crazy. So that's the first hurdle.

And then the second hurdle, a little rarer, is where they say, boy, it didn't help at all, or it's not helping enough despite me using it. And you believe them. They come in with a couple of empty canisters and you say, you really are using this medicine, or you refilled it three or four times. Then we know we have to go to that next level. When you think about that escalation step, how do you manage all the new options that we have along with the old ones?

Feldman: I like generic nonsteroidals. We've got topical tacrolimus and topical pimecrolimus. I like those. Then I think the newer things are excellent as well: topical ruxolitinib. I think it's at least as potent as triamcinolone. So in theory, you could use it as your starting therapy and as your maintenance long-term.

Now, we'd be remiss in not discussing alternative approaches because a lot of patients want them. I suspect a lot of your patients want them. What are you using?

Lio: I still use lots of steroids. I use a lot of systemic agents, all of those things.

But some of my favorites are topical coconut oil, which I think is pretty neat, because it actually has an antibacterial effect that's been shown. Admittedly, these are small studies that are not the level that we're used to for our medication, but I think they're fairly convincing. And it's thought that the monolaurin in there fights against staph in a pretty gentle way.

Another thing that I've been interested in is a topical black tea compress. This was a neat paper out of Germany, where they had patients with facial dermatitis. They included both atopic dermatitis and allergic contact dermatitis together.

They had patients just basically brew up a cup of tea, and I have my patients refrigerate it. I don't want anyone to put scalding hot tea on their face. But taking a little washcloth and a cool compress to the area a few times a day made a dramatic difference.

The last thing I'll put a plug in for is that I'm a big fan of vitamin D supplements. When you look at the literature, it's up and down and up and down. But I think there's a signal there. My thinking here is that there probably is a subtype of patients that actually do get a modest improvement with vitamin D. I just can't tell who.

And because it's relatively safe and because we all live in colder climates up here in Chicago, where we barely see the sun, I feel like it's not a crazy thing to give a very sensible vitamin D supplement — but not a crazy megadose of vitamin D.

Feldman: Very nice. Now, I could be mistaken, but I think I also learned about using topical vitamin B12 from you.

Lio: Yes. That's another one of my favorites, especially for the babies, because we know while we have crisaborole, our topical phosphodiesterase-4 inhibitor down to 3 months of age, that's the only one. And I see newborns and 1-month-olds. We have trouble getting things for them.

And here is a topical vitamin B12 preparation, very simple. We have it compounded locally for our patients. It really did seem to make a difference in two papers: one that looked at adults and one that looked at kids and adults. And I think it's fairly convincing — again, not a huge magnitude of response, but I think there's something there. The thinking here is that it's slightly anti-inflammatory and helps prevent flare-ups.

Feldman: How about systemic therapy? What is your go-to approach?

Lio: I feel, in the past few years, that everything's been turned upside down. When I got into this, we didn't have anything that was FDA approved. So we were using all of the old-fashioned immunosuppressants: cyclosporine, methotrexate, azathioprine, mycophenolate. And they certainly work. It's just there are lots of caveats with them.

Since 2017, with the advent of dupilumab, that's changed everything. For me now, that is my number-one go-to if I can. If the patient can get it, if they're not too needle-phobic, it's been a game changer. Same for you, would you say, Steve?

Feldman: Yeah, and I don't even think we have to talk about dupilumab because it's so effective and so safe. There's really nothing to say. I don't do any lab monitoring. I just give them the drug, and they do great. But then there's the few patients who don't do great on it. Are you using Janus kinase (JAK) inhibitors?

Lio: Yes. Weirdly enough, while my native population group that I'm escalating to dupilumab, my experience has been really favorable; 80% or 90% of them are doing pretty darn well, though not perfectly and there are certainly some side effects. But now, I'm getting a lot of referrals from a broader catchment area of people saying, gosh, we tried the dupilumab and it didn't work, it didn't work durably, or they had a side effect. We need the next step, and that's where the JAK inhibitors have swooped in like a superhero and have saved the day.

In particular, I probably have a lot more experience with upadacitinib (although I think abrocitinib is very, very similar), mostly just because I think upadacitinib is maybe just a touch stronger. For this group, I want to do everything we can to get them better. Thus far, I've seen really good improvement and really rapid improvement — almost prednisone speed, if you will.

In just a few days, people say, wow, it's turning around. I'll be curious as to how you think about the monitoring and safety of them and how you might counsel your patients on it.

Feldman: I think we need to do some laboratory monitoring. I don't know that I have a really well-defined checklist yet. I think about getting people up-to-date on vaccinations, maybe getting them a shingles vaccination and getting basic bloodwork, complete blood cell count (CBC), tuberculosis (TB) test, maybe a hepatitis panel.

Lio: Me too. That's exactly what I do. And that's how I tell it. I say annually — at the beginning and annually, we're going to do exactly that. Especially the TB, because a lot of insurance companies will say, you have to actually send it. It's annoying, but I get it. So we can show them that yes, we did the test, and we can say that the patient negative.

Then, usually at the first month, I'll do a CBC, a metabolic panel, and a lipid measurement because I think at least some studies have shown that lipids can be elevated in that first month and then, usually, every 2-3 months for a bit. And if things are really looking good, I have a patient now to whom I'm saying that we can check in maybe in 4-6 months because everything's been so stable.

I do still worry about some of these more vague potential side effects that we saw described in the tofacitinib trial. It's a different drug, a different JAK inhibitor in a different disease state: patients with rheumatoid arthritis over 50 years of age with a known cardiovascular risk factor. That was a particular study looking at that drug and its safety signal. That's where we got this, I think, pretty daunting black-box warning that talks about cancer. It talks about blood clots. It talks about major adverse cardiovascular events. It even talks about an increased risk for mortality.

For me, the hard part is when a patient says, well, gosh, I hear what you're saying. But what does it mean for me, taking a different drug in the same category and same class, but a different drug for a different condition, and I'm not a 50-year-old plus person with a cardiovascular risk factor? My answer is, I don't know.

But everything we have points to the fact that it's probably not going to be anywhere near the risks we're seeing in that population, because we really think that the data that we do have for this drug and its close cousins, abrocitinib and upadacitinib in atopic dermatitis, are pretty reassuring — although, admittedly, they're limited and relatively short-term. These drugs are fairly new.

Feldman: You go back to that tofacitinib study, and if I'm not mistaken, there was no statistically significantly greater risk with tofacitinib for, say, heart attacks than with the comparators, the tumor necrosis factor (TNF) inhibitors. They just couldn't show that it was as safe. The rate was higher, but it wasn't statistically significantly different.

Moreover, you wonder whether the TNF inhibitors are lowering people's cardiovascular risk. The tofacitinib may not even increase the risk at all. We're a step away from that because the upadacitinib and abrocitinib aren't really in the same class, because they're not blocking the same JAKs.

But that label is there. And I'm sure, in Chicago, that patients are asking that question, and dealing with that question may be the hardest aspect of this.

Lio: It really is. I think part of the difference is what we can say to our patients now is that we don't know, but we're going on that journey together. I'm going to be here with you. We're going to be following along closely with these labs.

This is really the drum that I beat most loudly: If we select the patient correctly — the patient who is miserable, who is really suffering from their disease, and who has tried those things leading up to it — I think it's a pretty easy sell because I say, listen, I can guarantee you one thing. I can guarantee you with 100% certainty that your atopic dermatitis will make you absolutely miserable enough that you'll be in my office today.

And they chuckle, and they say, you're right. Here I am. I didn't advertise. I'm not trying to put it in the water or have everybody take it without needing it. But for the right patient, I think it's a really important fit. That is, I think, the magic of that patient-doctor relationship.

Feldman: Before I let you go, is there anything on the horizon that you think is going to further change the game of atopic dermatitis management?

Lio: I do. There are a couple of new biologics coming, another interleukin (IL)-13 class inhibitor which, I think, will be neat. The IL-31 inhibitor being developed, which is kind of neat, the "master itch" cytokine. And then we have some new topicals that are currently available in psoriasis but are making their way to atopic dermatitis: tapinarof and roflumilast.

I'm really excited about these to have more nonsteroidal options because my patients especially are like, no steroids; we don't want them. And all the options give me some chances to find something that might be a perfect fit for a patient.

Feldman: If they'd make a topical that you only had to put on once a month, I'd be more excited about it. It's a pleasure talking with you.

Lio: Likewise. Thank you so much.

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