Conversations in Atopic Dermatitis

Upadacitinib, a novel JAK inhibitor, induced clear or almost clear skin among many adults and adolescents with atopic dermatitis.  

Emma Guttman-Yassky, MD, PhD, chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, spoke with MD/ alert about the research and the significant impact this drug could have on patients if approved.  

What was the idea behind this research? 

The idea is that we have a very large patient population with the atopic dermatitis or eczema, both adults and adolescents. And right now, we have only in terms of oral medications, we have first of all only one oral is approved for atopic dermatitis and that’s oral prednisone that is really not safe to give for more than a few days.  

And I myself never give it actually, because the moment you stop it, it perpetuates the disease, and everything comes back. And there are some other orals being used, but these are immune suppressants that have a very hefty safety concerns. So right now, while we have a really good biologic agent approved a little more than 4 years ago for atopic dermatitis, dupilumab, we really lack oral treatments. And oral treatments we also need because they have the plus of stopping and restarting at any time. And you know also there are patients that do not want a biologic.  

How was the study conducted? 

This was a very large study, phase 3 needed for, you know, approving a drug. In fact, two phase 3 studies. And they took two doses of the drug, 15 mg and 30 mg as compared to placebo.  

This is a JAK-1 antagonist, so specifically targeting a JAK-1 pathway. And patients were given the drug for 16 weeks orally every day. And what was very clear is that very early in the game, patients already responded. First, they each went down significantly within days. And then the disease severity to the point that at four weeks the majority of the efficacy was already attained. And then it was maintained up to week 16 and interestingly enough, not only with the high dose, but even the second dose had remarkable data among the very best that we've seen so far.  

What were your findings? 

The study found really great efficacy. This is perhaps the best efficacy we have so far for atopic dermatitis in both adolescents and adults, and very quick efficacy. So, the drug started to work really fast, particularly on the itch that is so important. You know it keeps patients up at night. But also on the red lesions. And so very quick efficacy on both the itch, but also the disease severity. 

What does it mean to have a drug that can help these patients quickly and effectively? 

What it means is that it gives them flexibility because you can take it for a few days. You can Stop it. That's something that is a plus of an oral medication. And, you know, the other thing that means for many patients that see a needle and they faint, and they cannot tolerate a biologic, they will be able to have a drug that will be efficacious for them that they couldn’t have before. 

Are there safety concerns for the treatment?  

It’s a JAK inhibitor, and JAK inhibitors have some safety issues. It did have some acne signal or acneiform lesions, and some infections. Not many. And it wasn’t significant compared to placebo. And some CPK elevations CPK the muscle enzyme and some lab abnormalities, but overall, I would say that this is a population that is young and healthy. The atopic dermatitis population, more than the arthritis population. So overall, I would say that the safety profile was good.  

Where does the research go from here? 

First of all, we need to approve the drug, see how it's actually picking up in practice. You know one thing is in clinical trials. We need to try it on our patients after clinical trials.  

And, in terms of atopic dermatitis in general, you know, generally we need more drugs. This is the most common disease, inflammatory disease in general, not only in skin. So, definitely we need more drugs. It’s 7% of the American population with atopic dermatitis and a third of these will have moderate to severe disease. So, you know, It’s a sizable number. We need to have choices and a larger tool box.  

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Etrasimod, a once-daily, oral S1P receptor modulator, resulted in a significant improvement in clear or almost clear skin among patients with atopic dermatitis, according to late-breaking data presented at AAD VMX 2021. 

Emma Guttman-Yassky, MD, PhD, chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, spoke with MD /alert about the research.  

What was the idea behind the using this inhibitor to treat atopic dermatitis? 

It’s a very novel concept with this treatment. It is preventing basically the lymphocytes or immune cells to go to the skin. Basically, it keeps them out of the skin and as you know, in skin diseases, I'm talking about skin diseases, but it's like that in many other target organs the money is in the target organ. In this case the skin, so it's basically preventing the inflammatory cells to go into the skin, and the idea is that it will reduce inflammation. 

How did you conduct the study? 

It was a short study, particularly for such a treatment that I think actually has more long-lasting effects in my view. So, I think a longer term will be beneficial. But this study was 12 weeks only in in which two doses were taken forward: 1 and 2 mg doses and the placebo arm. It was a small study and those doses and placebo were taken forward 12 weeks.  

There was a clear dose response, which is very encouraging in clinical trials, and clear differentiation from placebo. The clear or almost clear IGA 01 was significant at Week 12 and the change in EASI was not significant at week 12. But we need to remember that it was a short study. It did show a trend. But again it was very, very small numbers and the IGA of 01, maybe perhaps a better way it was obtained actually the response. And also this was during the pandemic and there were some patients that actually responded on the higher dose and due to the pandemic they did not come to visit and they were taken out of the study. And you know, in a small study that influences the study.  

So there was continuous improvement and I think it would have been much better later. But unfortunately, they did the study with an endpoint of 12 weeks. So I I hope that future studies will ascertain longer time points. You are absolutely right, and of course it needs a long-term extension so that we also learn about safety over time. You know that’s very important for us. 

What could this mean for patient care? 

The good thing about this drug, it's an oral and we need better orals. Right now we have as you know, one biologic that is the good biologic Dupixent approved for atopic dermatitis. But the atopic dermatitis is the most prevalent inflammatory disease so we need more. And we need orals. 

Were there safety concerns raised during the trial? 

The safety was actually good during the study. There were some decreases in lymphocytes. But this is something that is expected. This is the mechanism of action. Nothing concerning, and overall, I think it maintained a very good safety. 

Were there surprises in your findings? 

We need to remember that indications such as multiple sclerosis are very different than atopic dermatitis. And also this drug doesn't have some of the safety concerns like a cardiac issues that other in S1P antagonists have. But so far, in this patient population, I think atopic dermatitis patients are younger and healthier so far looks good. But of course we need longer term data. 

Disclosures: Emma Guttman-Yassky is an employee of Mount Sinai and has received research funds from Abbvie, Almirall, Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boerhinger-Ingelhiem, Cara Therapeutics, Eli Lilly, Galderma, Glenmark/Ichnos Sciences, Innovaderm, Janssen, KAO, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron Pharmaceuticals, Inc. and UCB; and is a consultant for Abbvie, Almirall, Amgen, Arena, Asana Biosciences, AstraZeneca, Boerhinger-Ingelhiem, Bristol-Meyers Squibb, Cara Therapeutics, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, Leo Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target PharmaSolutions, UCB and Ventyx Biosciences. 

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

A number of new atopic dermatitis treatment options are currently being developed that use different mechanisms of action and target different aspects of the disease in order to reduce symptom burden.

Amy S. Paller, MD, MS, Professor and Chair of Dermatology and Professor of Pediatrics, Northwestern University Feinberg School of Medicine spoke with MD /alert about the current atopic dermatitis treatment landscape, new treatments on the horizon, and the potential impact of these new treatments on clinical practice.  

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Patients with atopic dermatitis are at increased risk for infections, including rare but life-threatening systemic bacterial infections and eczema herpeticum.

Peck Y. Ong, MD, Associate Professor of Clinical Pediatrics at the University of Southern California and a physician at the Children’s Hospital Los Angeles, discusses his recent study on treating and preventing infections. 

What types of infections did you observe?

The result is from the skin infection first. So, because of the eczema, the pathophysiology, they have this allergic inflammation on their skin and that predispose them to have infection of the skin first. And then from the skin it leads to other complication. It leads to soft tissue infection, and then some of these patients also get a blood infection from the skin infection. Some gets bone and joint infection.

The life-threatening episodes are not common, but the invasive infection, like the blood infection or infection and another viral infection called eczema herpeticum. Those conditions can be life threatening. But they're not common. 

Can infections be prevented?

Because of our understanding of how eczema pathophysiology leads to infection and it's possible to prevent these infections. And because of a skin barrier defects because the skin is not intact in the eczema patients and also they have an increase of the allergic inflammation in the skin. So by targeting these areas, for example, to improve the skin barrier and also to target the allergic inflammation, we can prevent infection.

How do you treat infections and atopic dermatitis among children?

For the younger group for example from infants up to less than six years, basically what we have now is topical treatments, meaning topical steroid, topical calcineurin inhibitor and then crisaborole. So, those three are pretty much our approved topical treatments for that younger group of patients.

And so, if the patient has very severe eczema, have failed those three treatments, there isn’t much other options for those kids because we are always concerned with a systemic treatment for these kids, especially a systemic immunosuppressive.

And for the older kids, fortunately now in addition to those three topical treatments we have Dupixent, which is also now approved for over six years and above for atopic dermatitis.

What options do you have when these treatment fail?

For the acute flare, we do more intensive treatment like wet wrap, increase the amount of topical treatment, especially wet wrap we’ll use topical steroid. And again, we address a potential trigger. Whether it’s allergic trigger or infectious trigger. And obviously this is an area of need for more alternative therapy. So that’s why many alternative systemic agents are being studied in this group.  

What research still needs to be done?

You may have heard that dupilumab is being studied in this age group and there are several other systemic agents including oral JAK inhibitors that are being studied for this group of kids.

I’m encouraged by the work that’s being done now. We have seen great results from the older children already with some of these systemic agents. It’s very encouraging. It’s different compared to 15 years ago

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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.