Managing itch associated with atopic dermatitis is a critical intervention to patient quality of life.
Casey Butrus, PharmD: Dr Cameron, what’s the typical onset of action when you’re looking at a topical therapy vs a systemic therapy? Which 1 provides quicker relief for your patients?
Michael Cameron, MD, FAAD: Topical Opzelura [ruxolitinib] has data for itch relief within a week, which we’ve never seen. That has been my experience. When you go to the systemic side, we’re seeing itch relief with oral JAK inhibitors as early as 1 day after starting therapy. They work quickly, and that’s 1 of the most exciting things about oral JAK inhibitors. But their trial was designed to measure that as well. I’ve seen patients who go on Dupixent [dupilumab] and feel less itchy within a few days, but they weren’t looking at the end point the same way and designing the hierarchy like that statistically. All these systemic therapies provide rapid itch relief, which is exciting for patients, and Opzelura does as well.
Brian Keegan, MD, PhD: To add to that, some of the medicines we use very commonly, like steroids, like triamcinolone [Aristospan] and clobetasol [Clobex], were approved before probably all us on this panel were born. The studies were not necessarily even designed for atopic dermatitis, but some were designed for steroid-responsive dermatosis.
There’s a variety of information, but there are also large gaps of information. In older medicine, no one is going to fund specific criteria on that. We don’t necessarily even know how some of the old medicines compare with new medicines, which creates a challenge. There’s a cost basis that may drive decision-making, but it can still create challenges for how to give good guidance to patients when you think that steroid is going to work.
Casey Butrus, PharmD: You mentioned that some patients will experience itch relief within days. Do you notice the same thing with topical corticosteroids, or is that more of a delayed response?
Michael Cameron, MD, FAAD: I haven’t studied this, but it’s a little more delayed. If you think about the mechanism of action of a topical steroid vs Opzelura, for example, Brian Kim has done a lot of work to show how AD-related itch is propagated. There’s a reason why antihistamines don’t work for atopic dermatitis. It’s because AD-related itch is a nonhistaminergic pathway in the nerves.
With IL-31, the cytokine is directly involved in that nonhistaminergic itch pathway. Something like Opzelura blocks that right away. As soon as the cream goes through the skin barrier, IL-37 can no longer bind to the nerve endings and propagate that itch signal. I’m not sure a topical steroid molecule does that. I’m curious what you think, Dr Keegan. From my perspective, it’s a broad gun affecting inflammatory T cells. Some of that cytokine itch milieu can still propagate.
Brian Keegan, MD, PhD: As you highlight, I don’t know if the exact science is known, but there’s more of a cell-related response for those things. Some of those molecules can take days to weeks for them to work because you have to change the biology of the cell types that are within the skin that’s causing the inflammation.
Transcript edited for clarity.
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