Improving Quality of Life in Atopic Dermatitis With Targeted Therapies - Episode 7

Overview of JAK Inhibitors in Atopic Dermatitis

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Peter A. Lio, MD, provides an overview of emerging JAK inhibitors in the treatment of atopic dermatitis.

Linda Stein Gold, MD: Peter, we’ve talked a bit about the JAK inhibitors. Can you help us to understand, now that we’re talking about atopic dermatitis and this JAK-STAT pathway, why does that make sense?

Peter A. Lio, MD: It’s been so exciting. We heard a bit about the topical JAK inhibitor that has been in many ways the best of both worlds because we know when we’re targeting some of these cytokines, in particular IL-4 [interleukin-4], IL-13, which have come up a number of times, and even other ones that are involved, their common pathway for signaling the next step in the relay race, as I like to think about it, is through the JAK-STAT pathway. It follows that if we could go 1 level deeper intracellularly now, we could potentially disrupt that signal a little later and even capture more of those inflammatory signals all in one fell swoop. That’s what I think the promise of a JAK inhibitor is. In particular, we’re looking at these selective inhibitors that are trying to target in particular JAK1 a bit more than the other members of the JAK family. What they offer I think is almost steroid-like efficacy, reliability, and speed. And they have ability not to use the steroid and spare us from some of those potentially concerning adverse effects that we see with systemic steroids in particular.

That being said, the 2 oral JAK inhibitors that are now approved in the United States for atopic dermatitis, upadacitinib and abrocitinib, they’re both excellent. They’re very similar, but they also carry with them this black box warning. Now with the topical JAK inhibitor, I think we of course still have to discuss it. We have to go through it carefully with our patients, but it seems that the risks are in some ways less applicable because the overall exposure is so much less with the topical. When we’re putting someone on it orally, now we really have to talk about these. While I still think the absolute data are very reassuring when we see the actual numbers, in particular with our patients with atopic dermatitis, these things still happen. So, we have to go over the major adverse cardiovascular events. We have to talk about the malignancy risk, the infection risk. We have to make sure they’re being screened appropriately for tuberculosis and hepatitis. Then of course, we have laboratory monitoring that has to be done on an ongoing basis.

All that being said, for the right patient, these have been yet another level of game changing for me, especially for patients who either haven’t been able to get the improvement that we hope and dream of on a biologic agent, or they’re not a good candidate for a biologic for whatever reason. In those patients, in some ways, they’re the worst of the worst, talk about having really the end of the line here. The JAK inhibitors have still been able to deliver in my hands tremendous improvements in quality of life and with a rapidity that I think we almost only see with a steroid; we’re talking on the order of days. I had a patient who, while we were chatting about it, I try not to be too pushy because of all the potential issues with these and I like them to think about it. But as I brought in the sample, the patient opened the sample bottle and took the first pill in the room with me. And I said, “You are ready to go,” because she knew it was going to kick in soon.

Transcript edited for clarity