Q&A: Reframing JAK Inhibitor Safety and Flexibility in AD With Leon Kircik, MD

Leon Kircik, MD

In a recent interview at the 2025 Revolutionizing Atopic Dermatitis Conference (RAD) in Nashville, Tennessee, Leon Kircik, MD, discussed key takeaways for clinicians from his session, “Janus Kinase (JAK) Inhibitors in Atopic Dermatitis (AD) Management." Kircik is the founder and medical director of DermResearch and Physicians Skin Care, both in Louisville, as well as clinical professor of dermatology at Indiana University Medical Center in Indianapolis and at the Icahn School of Medicine in New York City.

Q: What do you see as some of the biggest clinical advantages for JAK inhibitors in AD compared to traditional systemic therapies or biologics?

A: With the JAK inhibitors, we certainly know their efficacy and the early onset of action. Oral JAKs work fast. However, we know that there is a concern with the box warning. So, when you compare them to the biologics, of course, there is a concern with the safety of the JAK inhibitors versus the biologics.

Q: How are you counseling patients about the black box warning, especially in light of the broader JAK class warnings issued by the FDA?

A: There is a huge confusion about the patient population. As you know, the history of the black box warning is very important to understand and to explain to the patient. I think as health care providers, first, we have to understand ourselves, the history of it, and where it came from, and then explain it the patient. The box warning comes from a drug called tofacitinib, Xeljanz, and that drug was studied for rheumatoid arthritis patients, and the safety issues were raised because of the inferiority of the safety of tofacitinib in rheumatoid arthritis patients older than 50 years of age and at least with one cardiovascular event.¹

What that means is, basically, they picked the worst of the rheumatoid arthritis patients who were previously exposed to methotrexate, oral steroids, or other immunosuppressive drugs, and they compared that safety to etanercept, which is a very safe biologic. It was an inferiority study comparing the safety of Xeljanz versus etanercept, which was, in all honesty, expected. Now, when we look at our patient population, such as atopic dermatitis patients and oral JAK inhibitors, certainly you do not see the same safety concerns or problems, especially when it comes to topical JAK inhibitors that we have.

I was part of the study on ruxolitinib. I had more than 40 patients in the study for atopic dermatitis. I always tell patients that unless they’re eating the cream, they have nothing to be concerned about. The absorption is very low with topical ruxolitinib, and it's certainly not a concern. But according to the agency, it's a class effect, and we see that class effect everywhere. Ironically, when you look at oral ruxolitinib that has been approved years ago for myelofibrosis, it doesn't have the box warning. So, it's quite ironic that oral ruxolitinib doesn't have a box warning, versus topical does have one, but that's because of the class effect and what happened with tofacitinib.

Q: What JAK inhibitors did you highlight during your meeting at RAD?

A: I discussed abrocitinib. Andrew Alexis, MD, MPH, discussed upadacitinib.² I was again an investigator for abrocitinib for an atopic dermatitis study, and we have participated in a couple of different studies with abrocitinib. It's approved for atopic dermatitis in patients aged 12 years and above. We studied the drug both for 200mg and 100mg. Certainly, 200mg is more effective than 100mg. Across the world, except in the United States, the approval is to start with 100mg, and then if you don't see efficacy, you can go up to 200mg after 12 weeks. Now, the most important label change happened recently. Now they removed the 12-week limit, you can go up to 200mg the next day if the treating health care provider seems to deem it appropriate. I think that's a big advantage. Now we have much more flexibility with abrocitinib, and I think that's going to be a very important change in the label, and give us more flexibility.

Q: What do you feel this change for abrocitinib could mean for clinicians and for patients with the condition?

A: I think it's going to be much more helpful. Abrocitinib works fast, especially when it comes to itch. When I give a sample to the patient, they call me before they get out of the car to say, "What was this that you gave me that my itch is almost gone now?” Unfortunately, the reverse side of it is when you stop the treatment, just like any other JAK inhibitor, the half-life of the drug is so short that unfortunately, the symptoms do come back quite fast, unlike the biologics.

References

1. FDA approves boxed warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib. US Food and Drug Administration. Updated January 1, 2022. https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and
2. Alexis A. Kircik L. Janus kinase (JAK) inhibitors in atopic dermatitis (AD) management. Presented at: 2025 Revolutionizing Atopic Dermatitis; June 6-7, 2025; Nashville, TN.