Management of Type 2 Inflammation in Atopic Dermatitis - Episode 5

Overview of Systemic Therapy Options for Atopic Dermatitis

March 18, 2022
Peter Lio, MD

Neal Jain, MD

Marc Serota, MD

Matt Feldman, MD

Shared insight on the systemic treatment armamentarium for atopic dermatitis and how it has evolved in recent years.


Peter A. Lio, MD: That’s exactly the way I build to that next level: we’ve tried our topicals, we’ve given it a go, but we’re not where we need to be. No matter how they look, that’s 1 of the disconnects where you expect a severe patient to be covered. Sometimes they don’t look that bad, but we’re not maintaining their quality of life. Or they’re miserable with an itch, or they’re using so many topicals that it’s now not safe. All those reasons might make me say it’s time for a systemic agent.

Historically, we’ve had our conventional immunosuppressants: methotrexate, cyclosporine [Neoral], mycophenolate, azathioprine [Imuran], and of course prednisone. But we try to avoid [these drugs] because you often get in such a bad cycle. More recently, in 2017, we had our first biologic agent with dupilumab [Dupixent], a IL-4 and IL-13 blocker, which is important and has changed things. At the end of 2021, we got our second biologic agent approved, and that is tralokinumab, similar to dupilumab, but these bind directly to IL-13, a cytokine-binding antibody. Then we also got our JAK inhibitors. Two oral JAK inhibitors with upadacitinib [Rinvoq] and abrocitinib [Cibinqo]. The third 1, baricitinib [Olumiant], is still not approved. I’m not sure what its status is, but we got those 2 of that class.

What’s amazing about these medicines is each is different. They have different safety and efficacy time courses. When you’re talking about these things—and I know this is all new—how are we thinking about some of the adverse events in the counseling about risks for these systemic agents? Dr Jain, would you start us off a little? When you’re talking about some of the systemics, how do you counsel?

Neal Jain, MD: It starts with going back to this shared decision-making: Are my patients satisfied? What level of risk are they willing to accept? You brought up a good point about uncontrolled AD [atopic dermatitis], which isn’t without its own risk. That’s especially important in our younger population. The more chronic the disease is, or the more severe the disease is early in life, and the longer you let it…burn, the more likely it’s going to be longer term and become chronic and lasting. Potentially, as you said, lead to some of those other type 2 inflammatory diseases, whether it’s allergic rhinitis, asthma, etc.

You’re grounded in that, and you say, “My goal for you would be this. What’s your goal, and how do we get there?” We’re fortunate that we have changed the paradigm a little with medications like dupilumab and other biologics, like tralokinumab and now the JAKs. I explain to them, “This is what we know about these drugs.” The risk may be different in each individual. We evaluate: “What’s the risk tolerance that you have, and what’s your goal?’ It’s this balancing act that we all play: “We know cyclosporin [Neoral] isn’t the drug for you because you have some mild renal disease or something of that nature,” or “You’re worried about hair loss, numbness, or other things.”

We think about those things, and we talk about those things. Are you someone who has a history of some infections? Do we want to use something that might increase that risk? With some of the newer medications, are you willing to accept that we don’t know everything there is to know, and what might happen with long-term use of these therapies given that this is a chronic disease, and that you may have the severe disease by the time we’re getting to those types of therapies?

Peter A. Lio, MD: Dr Feldman, in your practice, when you’re talking to patients about systemic agents, do you approach it in the same way?

Matt Feldman, MD: Absolutely. Also, I try to let the patient drive the conversation. As an allergist, I’m not as concerned about an injection vs oral medication. Most of my patients aren’t even educated about these different therapeutic options, and they honestly think I’m going to put them on standard allergy shots, so they almost get surprised when I start talking about other options.

The patient needs to drive the conversation, ask what their goals are, ask what their fears are, be very aware of their other comorbidities—from not just an atopic standpoint but a health standpoint. That can help drive the conversation where you can meet in the middle. If somebody says, “I’d rather get a shot every 2 weeks than have a risk of a blood clot,” that’s a screaming endorsement for 1 option vs another vs a patient who says, “I’ve tried that shot, and it didn’t work,” or “I don’t like the idea of injections, and I need to do anything to stop scratching. This is driving me crazy. My quality of life is in the tank,” as Dr Serota spoke about before.

These patients can have a horrible quality of life when they have severe disease. By listening to the patient and letting them drive the conversation a little…we can come to a reasonable conclusion most of the time.

Marc Serota, MD: There are a few reputable resources that I recommend for patients when they want to get more information about the systemic therapy options. If they’re a little more savvy, I really like the up-to-date articles. I’ll send that to the patient in their email and let them read through the different options. Some patients have pretty good medical background knowledge or are more educated patients and they want more nitty-gritty details. Otherwise, I’ll send them to the American Academy of Dermatology website or the American Academy of Allergy Asthma and Immunologywebsite, where they have very nice summaries for patients that are digestible to understand what the different therapies do.

It’s very important when you’re explaining these things to patients to start by using an analogy. I tell patients, “Your immune system in your body is like the military. “You have the Army, the Navy, the Air Force, and the Marines.” Occasionally 1 part gets it wrong and starts attacking something that’s a normal part of your body; those are autoimmune diseases. Or it starts reacting to something that’s a normal part of your environment, and those are the allergic diseases.

When that happens, we want to turn off just that part of the military that’s getting it wrong and leave the rest of the immune system alone to do its job. Before we had the newer medicines, we would give you something that suppressed the whole military. Now we can jam the radio signals of that battalion that’s getting it wrong. All the soldiers are still there. They’re waiting to make an attack, but they never get the “go” signal because we’re jamming their radios. As long as we keep doing that, your disease will be in the background.

If you explain it that way, then when you say, “There’s a shot I might want to give you,” there’s much more understanding of why that might be the better option…. I love using analogies to put it in a perspective that the patient can understand.

Transcript edited for clarity.