Expert Perspectives on JAK Inhibitors in Dermatology Care - Episode 3
Drs Jerry Bagel and Brett King discuss safety considerations and the clinical impact of how boxed warnings for JAK inhibitors highlighting how they affect physician decision-making.
Jerry Bagel, MD, MS: Back to tofacitinib, which seems to have issues if you increase the dose to 10 mg. That’s more of a PAN or JAK1, JAK2, JAK3 inhibitor. Do you believe there’s a safety difference between blocking a JAK1 vs a JAK 2 vs a JAK 3 vs a TYK2?
Brett King, MD, PhD: This is what everybody wants to know. We love the idea, but the answer to that question is what does the safety profile of JAK inhibitor X look like in a specific disease? We should be chasing after clinical trial data to answer the question. We shouldn’t be trying to address it at a higher level by talking about JAK selectivity; that’s a theoretical concept. Fundamentally, if at the end of a clinical trial of 1000 or 2000 patients, we see adverse events 1, 2, and 3, then it doesn’t matter how selective the JAK inhibitor was. If those were adverse events that we don’t like to see and may be associated with JAK inhibitors, then it doesn’t matter if I told you that it was highly selective. The adverse events happened. We should all focus on clinical efficacy and safety data for any of these drugs in different disease states and not talking about theoretical concepts of selectivity.
Jerry Bagel, MD, MS: If you look at abrocitinib in atopic dermatitis, you’re looking at the safety profile in the 2000 people in clinical trials. Yet the package insert talks about thrombophlebitis, gastro perforation, lymphomas, or tuberculosis. Do you think that’s extrapolated from abrocitinib in psoriatic arthritis and rheumatoid arthritis, in combination with methotrexate and systemic steroids, that data are brought into monotherapy? Or can you separate the clinical trials in atopic dermatitis where the comorbidity profile is much different from rheumatoid arthritis or psoriatic arthritis? Can you extrapolate a little on that?
Brett King, MD, PhD: This is hugely important. All JAK inhibitors, including ruxolitinib cream, have the same boxed warning for malignancies, serious infections, mortality, thrombosis, and major adverse cardiovascular bends. They all have the same label. One is topical. The safety data we have from clinical trials in, say, atopic dermatitis in alopecia areata don’t necessarily bear out those different elements of the boxed warning. But we still have the boxed warning. The boxed warning is taken from a large postmarketing study of tofacitinib in patients with moderate to severe rheumatoid arthritis, aged 50 years and older with at least 1 additional cardiovascular risk factor. One hundred percent of the patients in that postmarketing study were taking methotrexate; 57% of them were also taking prednisone. The average BMI [body mass index] in that study was 30 +/- 6. Your question is hugely important. As a community of dermatologists, we have to understand and recognize that the boxed warning is borrowed from a study that doesn’t approximate our patients and doesn’t approximate the way we treat our patients in dermatology. However, it’s the set of warnings that we have.
Jerry Bagel, MD, MS: Does it give you pause? For instance, you have a 26-year-old female patient with atopic dermatitis who is on birth control pills and smokes cigarettes, and she’s itching like crazy. You want to get her better tomorrow. You have Dupixent [dupilumab] that you could give her, or you could give her Rinvoq. As opposed to the woman who’s 26 years old, not smoking, and not on birth control pills. Would you put 1 on Rinvoq and the other not? What would you do?
Brett King, MD, PhD: I’m going to follow the label. The label is for the 2 oral JAK inhibitors in moderate to severe atopic dermatitis for use in refractory disease in patients who have failed previous systemic therapies, including biologics.
Jerry Bagel, MD, MS: Unless otherwise indicated.
Brett King, MD, PhD: Unless it’s inadvisable. That’s for sure. That’s the sentence, or the part of the label that, in some ways, gives us a little more ability to practice the art of medicine. Fundamentally, we need to make decisions together with our patient—shared decision-making. I still think we’re going to largely abide by that label. If we have a drug, like dupilumab, with no screening requirements, no lab requirements, and essentially no warnings but that is highly effective, we’re usually going to start there.
This is where oral JAK inhibitors are going to advance the care of our patients with atopic dermatitis. It’s miserable to be itchy. Just because somebody is better, that’s not good enough anymore. We want patients to be clear or almost clear. We want patients to have minimal to no itching. When we don’t get there with dupilumab, we need to start asking, “Should we advance to an oral JAK inhibitor?”
To your question: the 26-year-old who smokes and is taking the birth control pill, is she a candidate? Absolutely, because the data in the abrocitinib clinical trial and the data in the upadacitinib clinical trials do not show that she is at risk. They say nothing that we should be avoiding the birth control pill.
Transcripts edited for clarity