Expert Perspectives on JAK Inhibitors in Dermatology Care - Episode 5

Efficacy and Safety of JAK Inhibitors in Atopic Dermatitis

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Brett King, MD, PhD, shares insight on the dosage efficacy of oral JAK inhibitors abrocitinib and upadacitinib in atopic dermatitis.

Jerry Bagel, MD, MS: Going back to atopic dermatitis, there are 2 JAK [Janus kinase] inhibitors that are now orally FDA-approved for the management of atopic dermatitis. Would you please discuss the differences in efficacy or safety in these 2 molecules?

Brett King, MD, PhD: We have abrocitinib and upadacitinib, and most importantly, there are 2 doses of both. For abrocitinib, there’s a 100-mg dose and a 200-mg dose. Upadacitinib has a 15-mg dose and a 30-mg dose. The label says to start with the lower dose and if inadequate response is not achieved, increase the dose. Because there are 2 doses—and this is often true, we just talked about this in alopecia areata—often with JAK inhibitors, you give more. It’s a little bit different than the biologics, which are often 1 size fits all. When we think about the efficacy of abrocitinib and upadacitinib in moderate to severe atopic dermatitis, we’re really looking at achievement of clear or almost clear achievement of an IGA [Investigator Global Assessment] score of 0 or 1. Depending on the dose, 40% to 60% of patients over the course reach the primary end point, 12 week or 16 weeks, but also typically maintain at much longer time periods, up to a year. An easy way to think about this is efficacy similar to [dupilumab], out at 24 to 26 weeks, again, depending on the dose of the JAK inhibitor. We have to recognize that just because we have similar efficacy out at, say, 24 to 26 weeks, similar efficacy among abrocitinib, upadacitinib, dupilumab, there are important differences. Abrocitinib and upadacitinib have very rapid onset of disease suppression, so we see itch evaporate in days or weeks. We see that probably 80% to 90% of responders get to clear or almost clear over 4 weeks, so there is a really rapid suppression of disease. But the curves for efficacy for abrocitinib, dupilumab, upadacitinib kind of line up out [at approximately] 24 to 26 weeks. This is a huge advancement, in that they are highly efficacious, but there are also really important differences that I think can come into play in clinical practice.

Jerry Bagel, MD, MS: Do you think abrocitinib clinical trial data are significantly different, or different than upadacitinib’s clinical trial data for atopic dermatitis?

Brett King, MD, PhD: If you do this comparison that we’re not supposed to do because there’s no head-to-head data or no head-to-head trial, you can look at the efficacy curves for upadacitinib and abrocitinib and you can say, boy, these look a little bit different to me.

Jerry Bagel, MD, MS: How so?

Brett King, MD, PhD: Mostly where the lines migrate to, how high on a 0% to 100% scale for achievement of easy 75. Upadacitinib seems to reach higher heights than abrocitinib, but this is the thing that I think is really intriguing: We do have head-to-head trials of abrocitinib versus dupilumab and upadacitinib versus dupilumab. For me, the transitive property must work here that, if at weeks 24 to 26, abrocitinib is similar to dupilumab and at weeks 24 to 26 upadacitinib is similar to dupilumab, then necessarily, abrocitinib must be similar to upadacitinib. I think that there are fewer differences than in some ways meet the eye.

Transcript edited for clarity