Moderate to Severe Disease: Systemic Therapy

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Transcript:

Lawrence Eichenfield, MD: Let’s step it up from our general measures. Let’s transition to moderate to severe disease and younger children and in adolescents to a degree. I guess the question, Fred, is how do you define moderate to severe disease in pediatrics?

Fred Ghali, MD:In the real world, when you walk into the room, you need to take into account how much body surface area could be involved. Maybe you have a patient who has 15% to 20% of their body surface area involved; that plays a role. Also, you have to take into account the way those lesions look. Is there a lot of oozing, crust, excoriation? I also take into account the quality of life. Has there been a big impact on sleep disturbance or school performance for the family members in the house? It’s tricky sometimes. We alluded to it earlier: You could have wide body surface area and mild disease. You could have localized disease on the exposed area of the hands or face; that’s moderate disease as well. You have to look at all 3 of these things: How much of the body is involved? What do the lesions look like? What is the impact on quality of life? That helps you develop an overall impression.

Lawrence Eichenfield, MD: I always want to have an eczema A1C, a glycated hemoglobin. Your integral sum of how disabling or how impactful the eczema has been, or even just a critical severity of symptoms. We don’t have that, but it’s an important one. Elaine, when do you consider systemic therapy for moderate to severe disease? What’s your algorithm?

Elaine Siegfried, MD: Of course, that’s the corollary to what is moderate to severe. It’s really a euphemism for who needs more aggressive systemic treatment? It’s probably been 1 of the more rewarding parts of my career, to finally have some other options, where the safety and efficacy are good for people who have moderate to severe disease. There are a lot of things that contribute to why I would put someone on systemic therapy. They’re beyond topical therapy, they can’t handle it, they can’t tolerate it, they can’t get access to it, they’re using too much of it, they’re still not getting quality control of their disease. All those things play a role.

Lawrence Eichenfield, MD: Anyone want to add? You really hit the hallmarks on it. We also consider if we have adequately considered secondary infection, contact dermatitis in that patient. Have they had phototherapy? Can they get phototherapy? We work our way up to systemic pretty quickly. Let’s move over to discuss that. Peter, what’s your sense of the short-term and long-term safety concerns for systemic therapy in adolescents and then in younger kids as well?

Peter Lio, MD: With our conventional immunosuppressants, the ones mostly used are Prednisone—although we try to avoid that at absolutely all costs—cyclosporin, methotrexate, and potentially azathioprine and sometimes mycophenolate mofetil. Those are the main players, we briefly mentioned phototherapy. Phototherapy is a little different. I find that to be pretty safe, but it’s clunky and difficult to get families and patients to come to the office, and it can be very expensive even if it’s covered. They’re having a $50 co-pay 3 times a week. That’s my preference for these younger guys if I can. But if I can’t, then I have to pick 1 of those conventional immunosuppressants.

Unfortunately, they all have quite a few different adverse events, both in the short term. Prednisone has blood pressure spikes. Even in the last couple of years, I’ve had patients referred to me because they had mania from the Prednisone. They weren’t sleeping, they were going crazy—behavioral stuff, and you realize even that 1-week taper can be a serious issue. We have of course vascular necrosis. Then the longer-term issues are significant with Prednisone and its cohort. For cyclosporin, it’s short term is fairly safe. It is a Prednisone-sparing agent, so it’s really safe. But we know as soon as we start administering it, there is some kidney damage, at least microscopically. We are watching those kidneys every month. It can be traumatic to have kids come in for labs over and over. Of course, their blood pressure can go up on cyclosporin. A couple of kids I’ve had over the years have been on it for a few months, and they developed hypertrichosis all over their face. I had 1 little guy who everyone was calling a wolf man at school; it was terrible. Of course, there is also gingival hyperplasia. Mycophenolate is probably among the safer options. It really does have a pretty good safety profile, but upset stomach is very important, and I often feel like you trade the safety and efficacy pretty clearly. Mycophenolate is in my hands in methotrexate. It takes several months to kick in. We’re watching the liver, and nausea is another issue. In my experience, it’s not that helpful. Until a few years ago—in 2017, we had our first biologic introduced for adults, and it got approved in 2019 for adolescents just this year in children—we did not have a lot to lean on.

Lawrence Eichenfield, MD: That’s reasonable. And then, with COVID-19 [coronavirus disease 2019] going on, it makes it even trickier to consider traditional immunosuppressants. There are probably some variations in terms of how much people are using traditional immunosuppressants versus moving over to dupilumab, which as we’re doing this has been approved both for adolescents and 6-year-olds, plus studies of earlier patients in process.

Transcript Edited for Clarity


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