Aaron Drucker, MD: Weighing Limitations in New Atopic Dermatitis Drugs

Aaron Drucker, MD

Credit: University of Toronoto

Despite an acknowledged boom in available atopic dermatitis therapies, there’s reason to remain realistic about treatment capability and the comprehensive efficacy-safety profiles of each agent.

In the second segment of an interview with HCPLive at the American Academy of Dermatology (AAD) 2023 Annual Meeting in New Orleans this weekend, Aaron Drucker, MD, a dermatologist with the University of Toronto and Women’s College Hospital, discussed components of initiating and switching drug class options, comorbidity cross-benefit, and improving diagnostics to achieve optimal atopic dermatitis care.

HCPLive: Is there's any key advice you could provide to prescribing clinicians navigating comparative efficacy data across newer atopic dermatitis drugs?

Rucker: I think when when we look at the comparative efficacy of these agents, it stands out that the higher doses of the JAK inhibitors, upadacitinib and abrocitinib, they are the most effective agents that we have right now. But JAK inhibitors have some safety baggage attached to them, particularly from the rheumatoid arthritis literature, and tofacitinib. We know that those agents increase the risk of things like blood clots and cancers. And so, we have to be mindful that.

Our patients are not older rheumatoid arthritis patients with multiple comorbidities on average, but we do have some people that look like that. And our JAK inhibitors are not tofacitinib. But I think when we're thinking about starting a patient on these medications, we can't just look at the efficacy data on its own. We should pair that with what we know about these different classes of medications and their safety data, and give patients a global sense of these medications' relative efficacy and safety issues, and help them make a decision.

Is there any development in discussion around switching with these agents as well?

I think for most of our patients who are thinking about starting a systemic agent, the first line agent is going to be dupilumab. It's been around for a while now, we're comfortable with it, it's effective. We're comfortable with its safety profile. But for some people, it's not going to be effective in the long term, or it's not gonna be optimally effective. So, we might think about switching to something else, and then it's a real question of going to another biologic that might not be as effective like tralokinumab, or going to a JAK inhibitor that's potentially more effective but comes with more potential safety issues.

And I think that's where a discussion needs to be had. There's no right decision for every patient, and patients can make their make their own decision based on information that that you give them.

There's also a lot of talk about having someone on a JAK inhibitor to get them under control and then switching to something else. I do think that's reasonable. We don't have a lot of data to guide us there, but we know that the JAK inhibitors work quickly, that they're very effective. And so, if we can help to get someone under control then potentially transition them to something for a longer term use, that's a strategy that makes sense to me—even if we don't know exactly what that looks like in a large group of patients.

Obviously, we're seeing a really great marriage of fields across the allergic, pulmonary, sometimes gastric or rheumatic patient populations where these inflammation-targeting agents are cross-beneficial, and a lot of these patients are comorbid or presenting with a multitude of atopic diseases.

What sort of involvement do we see in understanding the full-patient profile when considering some of these pathway-targeting agents that could be "2 birds, 1 stone" beneficial?

We think about patients' comorbidities a lot when we're thinking about safety in medications. If someone has cardiovascular disease, that might put us away from a JAK inhibitor, but comorbidities can also help guide us to a specific treatment if we might be able to kill 2 birds with 1 stone.

So, if a patient has inflammatory bowel disease, and atopic dermatitis, we know a JAK inhibitor can work for both of those conditions. We might choose that same for arthritis and atopic dermatitis. Alopecia areata is a common comorbidity of atopic dermatitis. Many of our patients who have asthma, particularly a more severe asthma, a biological like dupilumab can be effective for both of those. So, again, these are things that we have to keep in mind: each individual person is different and is going to have different considerations when we're picking ways to start.

We've been talking a lot about informing the long-term treatment module, but obviously, initiation of these treatments also alludes to the continued need for better understanding of biomarkers, early disease presentation, and initiating timely, effective treatment. How do you feel about your field's current standard for diagnosing, screening, and initiating care?

I think I'm a personalized medicine skeptic. I think it would be really nice if we could know for a particular person who has bad eczema, that this is the drug that's going to work the best for them based on the ticket tape strip of their skin or their cytokine profile and their blood. I really don't think we're close to being there yet.

I think there's a lot of potential there, but we're really not there. And so, I think all we can do is base our decisions on the data that we have, which is based on average patients from clinical trials. And I think we still can get pretty good outcomes for most patients, but for some people, it's going to mean waiting a longer time to find the right medication for them, which is unfortunate but is where we are right now.