Experts in dermatology review currently available JAK inhibitors for use in patients with dermatological conditions and highlight their differences.
Jerry Bagel, MD, MS: A few JAK inhibitors are already available. In about 2 weeks, there’s going to be a TYK2 inhibitor available. Could you discuss a few of the available JAK inhibitors, what their treatment is, what their mechanism of action is, and how they differ from one another?
Brett King, MD, PhD: In our toolbox, we have ruxolitinib 1.5% cream. This turned out to be the first JAK inhibitor approved in dermatology in September of last year  for the treatment of mild to moderate atopic dermatitis and more recently for vitiligo. Ruxolitinib is a JAK1/2 inhibitor. We should talk about selectivity, what that is, and does it matter? In January , we had FDA approval of 2 oral JAK inhibitors for moderate to severe atopic dermatitis: abrocitinib, a JAK1 inhibitor, and upadacitinib, a JAK1 or JAK1/2 inhibitor. In June, baricitinib—another JAK1/2 inhibitor— [was approved] for severe alopecia areata. Then [in August], ruxolitinib 1.5% cream, got a second approval in vitiligo.
The idea is that we’re going to frequently hear that this is drug X, and it’s a JAK1 inhibitor, a JAK1/2 inhibitor, a JAK3 inhibitor, a TYK2 inhibitor, deucravacitinib, which we may see in psoriasis. The idea is that we have these 4 members of the JAK family: JAK1, JAK2, JAK3, and TYK2. The idea is that different cytokines signal through, or use 1 or more of these 4 JAK proteins to communicate their message to the nucleus. At least conceptually, you can have incredible selectivity for 1 of these JAKs, or you can be less selective.
Theoretically, you can dial in or narrow the spectrum of cytokines that you modulate with JAK inhibitor selectivity, which is less about narrowing the spectrum and more about trying to avoid off-target effects. It’s going to take some time before we understand how that happens and whether we can do that when somebody swallows a pill. The selectivity might wash away a little when somebody ingests a pill and it goes inside their blood.
Transcript edited for clarity