Q&A: JAK Inhibitor Safety in Context and the Rich Atopic Dermatitis Pipeline, with Leon Kircik, MD

Janus kinase (JAK) inhibitors provide rapid efficacy in the management of atopic dermatitis (AD) but present safety concerns for some heath care professionals because of the FDA black box warning across the class, a high-level precaution required following clinical trials of tofacitinib in rheumatoid arthritis.1

In an interview with Patient Care at Revolutionizing Atopic Dermatitis 2025 in Nashville, Tennessee, June 6-7, Leon Kircik, MD, clarified misconceptions around the boxed warning, placing the caution in context and then shared his excitement about the "very rich pipeline in atopic dermatitis." He met with Patient Care following his presentation at the conference, Janus Kinase (JAK) Inhibitors in Atopic Dermatitis (AD) Management.2 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.

Leon Kircik, MD

Patient Care: What was the focus of your presentation at RAD on use of JAK inhibitors for treatment of atopic dermatitis?

Leon Kircik, MD: We discussed all the JAK inhibitors, both topicals and orals and the benefits of this class, that is their efficacy and also their rapid onset of action. As you know, the JAK inhibitors do have a black box warning,1 which the biologic agents for atopic dermatitis do not, and we addressed that issue. We have to remember that the boxed warning is not based on experience with the JAK inhibitors that are approved for atopic dermatitis--topical ruxolitinib and oral upadacitinib and abrocitinib. There is still misunderstanding about the type of patients the warning is meant for. As the prescribers, we need to understand the origin of the warning so we can counsel patients correctly. The boxed warning stems from safety concerns that were identified in a study of tofacitinib (Xeljanz) in individuals with rheumatoid arthritis where it showed a less favorable safety profile in study participants who were older than 50 years and had had at least 1 cardiovascular event.2 So the patient population, and the conditions were totally different. However, the regulators consider this a class effect and so all JAK inhibitors, no matter the condition they are indicated for, carry the warning.

PC: In your experience, do you feel that clinicians are wary of prescribing JAK inhibitors?

Kircik: Yes, they are. There is always a concern for safety, and sometimes there are perceptions. I think the box warning doesn't help. But, it helps to understand what really the side effects are for the particular drugs that are approved for atopic dermatitis. In phase 3 clinical trials, the adverse effects that were seen were mild to moderate and they included acne, nausea, headache and some [upper respiratory tract infections].3 It is not helpful to look back at tofacitinib.

Ironically, the most common adverse effects I see in my practice with JAK inhibitors is acne. And that's something that I'm not really concerned about, because I'm a dermatologist; I know how to treat it. Of course I would be concerned about a cardiac event or a venous thromboembolism or pulmonary embolism. But, again, those are very, very rare. When you look at the numbers, you're looking at an incidence of 0.1 or 0.2 per 100 patient years. And if you do the math, if you write 1,000 prescriptions in 1 year, you may, may get one of those serious adverse events. But, honestly, we're not going to be writing 1,000, prescriptions in one year. The most important messages for a primary care clinician who's seeing patients with atopic dermatitis is that JAK inhibitors are efficacious. They work very fast for itching. On the other hand, they should be aware of the possible adverse events and, take precautions accordingly.

PC: In your session you mentioned that research on atopic dermatitis treatment right now is similar to where the science was 20 years ago with psoriasis.

Kircik: Atopic dermatitis is really, really booming. Most of my business is clinical study, and we have so many atopic derm studies going on. It was like this 20 years ago with psoriasis research but then the majority of the studies were on biologics. But for atopic dermatitis now, not only do we have biologics, but we have oral small molecules and we also have topicals. So we have these studies going on from every aspect, topical, oral, small molecules, and biologics.

And looking ahead, by next year we will probably have even more options and possibly medications that work via even more different pathways. I'm thinking of investigations into the JAK-STAT (signal transducer and activator of transcription) signaling pathway. That pathway is involved with inflammatory responses like what is seen in atopic dermatitis, and especially those that are mediated by type 2 cytokines. So inhibiting that pathway may be another avenue to treat the disease. So we have a very rich pipeline in atopic dermatitis. It's an exciting time.

For more RAD 2025 meeting coverage, please click here.

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.
3. Chovatiya R, Paller AS. JAK inhibitors in the treatment of atopic dermatitis. JACI. 2021;148(4):927-940. https://www.jacionline.org/article/S0091-6749(21)01298-7/fulltext