Pharmacological options for the treatment of pediatric atopic dermatitis

Joshua Zeichner, MD: For our last question, I want to focus on therapy. Let’s review the options we have for mild to moderate atopic dermatitis [AD], in terms of topical and systemic medications. Vikash, lead this for us. Walk us through topical options in terms of emollients or moisturizers and prescription options.

Vikash Oza, medical doctor: In terms of prescription options, our real reserve remains topical steroids. Although we have all of these newer therapies, topical steroids are still effective in treating flare-ups. Often, they can be cheaper in our health care system, and they play an important role in getting through a flare-up. Often patients struggle to maintain the chronic aspect of their disease, especially patients who come to see us. Most patients who see a specialist often have moderate to severe disease and need maintenance therapy. This is where we lean towards potentially non-steroidal options.

Depending on your age, you have different FDA-approved options. For infants 3 months and older, we have crisaborole, or Eucrisa. For children 2 years and older, we have tacrolimus 0.03% and pimecrolimus. For patients aged 16 and over, we have tacrolimus 0.1%. Our new agent for patients 12 years and older is topical ruxolitinib. We’re starting to integrate these therapies as disease maintenance, helping someone through a flare-up, but having a therapy that we think you can use on and off to maintain control of your disease if you don’t fall into this threshold to have a systemic disease disease.

As Raj mentioned at the beginning, the second pillar is skincare. It’s interesting that we have these directed therapies. With our skincare, we still don’t have therapies directed for their specific barrier issue because there’s probably a lot of variability. But a lot of what we have on the market are ceramide-enriched emollients, which are important as a mainstay. We have literature showing that the appropriate use of an emollient 2-3 times a day can potentially reduce the frequency of flare-ups. They are important.

From a clinician perspective, 1 thing I’ve emphasized a little less over time on my first visit with a patient with atopic dermatitis, when we’re trying to control him and get him out of a flare-up , is to focus on prescription therapies during these first few weeks, as they have already exhausted all that their pharmacy has to offer when it comes to emollients. Gentle skincare is clearly important, but getting them to the point where they’re above that bump of inflammation, where maintaining their skin barrier can help as a preventative way to reduce flare-ups, is conceptually a construct that I help guide them.

Joshua Zeichner, MD: Brit, let us wrap this up for us. Introduce us to some of the traditional systemic medications and newer biologics we have for atopic dermatitis.

Brittany Craiglow, MD: Thankfully, that conversation has changed a lot, even in the past few years. Before targeted therapy, we used a lot more chronic topicals, and vacillating patients would have their parents or themselves do a lot of homework just to keep them well, including wet wraps and all these things ; it’s like a full time job. There is data that caregivers spend about 22 hours per week with their child with atopic dermatitis. We’ve accepted this before because our options were those things that had a decent amount of associated risk. These were more traditional immunosuppressants, such as cyclosporine, mycophenolate and methotrexate. We would pull the trigger. But at least for me, I waited until I felt it was so bad that I could justify the risk and get the patient to have blood drawn and have a conversation about the risk of malignancy and infections, etc.

Having more targeted therapies made me realize that I was tolerating a level of illness that I probably shouldn’t have endured because the options weren’t that great. We have these traditional, broader-acting immunosuppressants. There are oral corticosteroids. It almost never happens in my clinic, unless I put someone in contact with something else, because we know it’s bandages. It’s a short-term solution. Unfortunately, many patients are still on chronic oral steroids – they go see someone who gives them intramuscular triamcinolone every few months, and we cannot underestimate the long-term risk. I have seen patients with osteopenia due to chronic oral steroids for their atopic dermatitis. We have to go beyond that. We don’t have to do that at all now.

With dupilumab, it was a major breakthrough to have targeted therapy not to mention a black box warning or having blood drawn. Now we have approval up to 6 months of age. If anything speaks of safety, even in our adult patients, it is that. Having dupilumab in my toolbox has allowed me to pull the trigger on patients earlier and have a huge impact on their quality of life. Earlier it was pointed out that people don’t even know how bad it is. It’s because they’ve always been like that. With psoriasis, people come in and say, “What is it? Make it disappear,” or someone has 5% body surface area and you say, “You need a biologic.” It’s because they had normal skin, then they got psoriasis and they want to go back to how they were before. But with AD, they know nothing different. We have to help people understand it. “Now there is something. I know things haven’t worked out for you in the past, or there have been some scary side effects. But now we have options.

After dupilumab, we have the IL-13 inhibitor tralokinumab, and we recently had 2 oral JAK inhibitors approved, with upadacitinib for patients aged 12 and over and abrocitinib for patients aged 18 and over. These therapies can be very effective and work quickly on the itch, but in my mind and according to their labels, they are second in line to a biologic like dupilumab. It’s more of a conversation because they work intracellularly and more cytokines are floating around there. There are more discussions about adverse effects and risks. But it’s amazing for patients, because while a lot of people will be fine with dupilumab, there will be some people for whom it’s not completely effective. For them we now have an option if they are 12 or older. But we’re also going to see trials in younger populations.

It is a disease that people will not have to live with. It took a while, but we’re going to be there very soon with psoriasis. What’s cool is that we started out with a great, super targeted safety profile compared to what we’ve had to do with biologics in psoriasis.

Joshua Zeichner, MD: When we look at the total patient population, in many ways it is easy to decide how to treat mild patients and severe patients. Even before we had more targeted therapies, it was worth taking the risk to get benefit for severe patients. But the people with the most unmet need were the moderate patients. These were people I personally gave a jar of triamcinolone to. They were fine, but they weren’t bad enough in my mind to warrant systemic immunosuppressive medication, like cyclosporine. But now we have targeted biologics that address IL-4 and IL-13 that have such a good safety profile – there’s a systemic agent that can change the lives of those moderate patients who previously I wouldn’t even have considered a systemic drug. In my practice, it’s a home run across the board, especially for moderate patients.

Brittany Craiglow, MD: Some of these patients are the most grateful, like the person who is not erythrodermic but just never clear. They can’t go on vacation without their triamcinolone. Everything is greasy. They then have a new life. We’re talking about therapies that have an excellent side effect profile. We shouldn’t wait for these people. If they come in and have 3 different prescriptions, and they have to use 1 that day and another on another day and they can’t keep up, and they wake up scratching, then we have to move on and deal with them more appropriately.

Joshua Zeichner, MD: For anyone listening to this, my message is to remember that the full indication for these systemic biologics is moderate to severe. Don’t forget those moderates, where we can have a huge impact on quality of life.

Transcript edited for clarity