Therapy Individualization for Atopic Dermatitis

Raj Chovatiya, MD, PhD: Maybe you guys feel different, but I’m figuring out how to balance these therapies across children, adolescents, adults, patients with more severe disease, and patients in that moderate range. What’s the best choice for them? You both highlighted 1 important distinction between some of them: age cutoffs. In the case of dupilumab, we’re talking 6 months and up. In the case of tralokinumab, it’s 18 months, but it will probably soon be lower. In some other markets, there’s adolescent dosing as well. In the case of oral JAK inhibitors, both are down to 12 years and up. In the case of our topical therapy, 12 years and up. There are many choices. It’s becoming harder to parse out the right circumstance to use these therapies for the right patient. George, how do you figure out the right treatment and the right patient? That’s a billion-dollar question.

George Han, MD, PhD: It’s tough, but it’s interesting. With psoriasis, you have this luxury—at least in clinical trials—to exclude unstable forms of psoriasis. We exclude guttate psoriasis or erythrodermic psoriasis. How do you handle it when your baseline disease state is unstable to begin with? That’s the tough part, especially when you have patients who come in and don’t have severe eczema all the time but have bad flares over the course of a year. It’s been a struggle for me to convince patients that they need to be on year-round therapy for something they see as more episodic.

One of the challenges with biologic therapy is that the rates of antidrug antibodies go up the longer you stay off these medicines. I’ve seen some of my patients who, during COVID-19, went off a biologic for atopic dermatitis. When they tried to go back to it, they got less of a response than they had the first time. That’s 1 case where if you’re looking for a biologic and the patient still wants a biologic, another medication such as tralokinumab could be helpful.

It’s interesting that we’re at the cutting edge of immunology and dermatology with these medicines. We’re learning things about the decoy receptor and tralokinumab blocks. There’s so much interesting science behind all these developments. We’re still constrained by our clinical trial outcome measures and the time we can keep patients on them. Medicine like tralokinumab needs a little longer to get up to full efficacy, but you can’t keep patients on placebo for more than 4 months, or 16 weeks. That’s the practical side of trial design. There’s a lot of nuance that we’ll hopefully figure out even with new biologics coming out. I still mostly place my patients on JAK inhibitors or patients who haven’t done well on dupilumab. That doesn’t just mean somebody who’s totally failing. There could be improvement in a large part of their body surface area, but there are some stubborn areas, often on the head and neck, where they’re not doing so well. They might be looking for another option to carry them the rest of the way.

Raj Chovatiya, MD, PhD: I like that because I feel that we’re constrained in some ways. It’s great that we have so many trials, but we think about atopic dermatitis relatively homogeneously in terms of the way we design our studies. That million-dollar buzzword is heterogeneous. If we’ve learned anything about the biggest differences between our 2 common diseases—atopic dermatitis and psoriasis—it’s that psoriasis is much more predictable in many ways. It’s a single linear pathway involved in almost every individual. For atopic dermatitis, even with our best therapies, not everybody reacts exactly the same way. It makes selecting that right therapy for the right patient a little more complicated. I’d love to get your take, Vivian. Do you have any tricks that help you connect the right patient with the right treatment?

Vivian Shi, MD, FAAD: Often, it’s trial and error…. But the profile of a patient doesn’t stay the same over time. I can give you an example: the flare factor is different. I have patients who previously flared only in the summer, but then environmental factors change. They move around the country, and the weather changes. Then they’ll flare in the winter if they’re in Chicago, for example. Even within 1 individual that changes. That leads to the seasonal or episodic nature of this disease. We don’t get to see that when a patient is on a biologic long term, assuming adherence.

The discussion of a drug holiday comes to up repeatedly in my clinic, but the beauty of oral JAKs is that we can do a drug holiday without the risk of an antidrug-neutralizing antibody. For patients who tend to have more stubborn disease, despite already being on a biologic, we need to know the rules before we break them, and the 3 of us are rule breakers in a way. Adding other oral medications on top of someone who’s already somewhat controlled on a biologic is another option to get stubborn areas, seasonal flares, or stress flares on top of that.

Raj Chovatiya, MD, PhD: That highlights real-world clinical practice. We may not necessarily have the disease subset in the way we want it, but now that we have more options, we can mix and match more treatments to get patients under better control.

George Han, MD, PhD: Context is so important. When you think about it, we give out prednisone tapers like candy. We do it all the time. If you step back and think about the risks of chronic steroid usage, there’s a long list of things that you don’t want patients experiencing. As Vivian said, wouldn’t JAK inhibitors be great in the short term? They work fast, and you can come on and off them because they’re small molecules. If your frame of reference is steroid tapers and heavier-duty immunosuppressants, they start to look less scary.

Transcript Edited for Clarity