Potential Role of JAK Inhibitors in Atopic Dermatitis Treatment - Episode 4

Efficacy and Safety of Systemic Agents for Severe and Persistent Atopic Dermatitis

Jamie L. McConaha, PharmD, NCTTP, BCACP, CDE, focuses on the safety and efficacy of systemic agents used to treat atopic dermatitis.

Peter Lio, MD: I’d like to shift gears and talk about the other end of the spectrum. If these are our topical agents, what about for those patients where we really have more severe and persistent atopic dermatitis? Our guideline documents usually will say we’re going to start very simply. We’re going to make sure everybody is using good gentle skincare, gentle bathing. We’re going to then jump up to that reactive approach. Maybe we’ll use some topical corticosteroids here and there, but if we find we’re not doing well with that, we might need to shift up to our nonsteroidal agents as we just heard. But what if all of that is not enough for any number of reasons? When we get to those patients who have more persistent and moderate to severe uncontrolled atopic dermatitis, then we have to bring out our systemic immunosuppressant agents historically, like methotrexate, azathioprine, and cyclosporine. Jamie, could you talk to us about those?

Jamie L. McConaha, PharmD, NCTTP, BCACP, CDE: Yes. Exactly as you said, these 3 agents are systemic agents that are usually reserved for when we have patients with moderate to severe disease, or patients who haven’t responded to some of the topical therapies that we just discussed. All 3 of these agents are older. There are lots of data on their efficacy, although some of them may not have specific data with atopic dermatitis but with other types of skin diseases, and I’ll talk about those in one second. But the issue with all of these 3 types of systemic agents is going to be the adverse effects. It’s not something topical that you’re just placing on your skin. It’s something the patient is doing orally, so you’re at a greater risk for those adverse effects and even sometimes rare adverse events that can be very detrimental to the patient. We need to keep in mind, too, that we’re using these or considering their use in mostly young children, so definitely something to keep in mind.

The first one that you mentioned was methotrexate, again an older medication. We’re all familiar with methotrexate. This is the one for which the true efficacy in atopic dermatitis is not necessarily known. There’s inconsistency among studies with regard to dosing and duration of therapy, though it has been used historically for treatment of atopic dermatitis for a number of years. Dosing is very patient specific. It’s a medication that’s given once a week, and it ranges anywhere from, I’ve seen 7.5 mg all the way up to 25 mg given once a week. But it’s the adverse effects with this; gastrointestinal [GI] adverse effects are common, nausea. Then some of the severe ones that I had alluded to earlier can be things like bone marrow suppression, pulmonary fibrosis, etc. These are all things that would definitely be monitored for if we had a patient on methotrexate therapy.

Our second systemic agent is azathioprine. For this one, our guidelines, the American Academy of Dermatology [AAD] guidelines recommend this as an option for refractory atopic dermatitis. It’s not going to be one of our first-line agents. We do have studies again that showed it is effective in atopic dermatitis. The dose ranges based on the patient. But again, some of the systemic side effects that you’re going to see with this medication is GI adverse effects. Nausea, vomiting, bloating, anorexia, cramping, all of those GI adverse effects that patients don’t want to experience. Headache is common. Patients can have hypersensitivity reactions to this medication. Some of the more serious adverse effects would be things like leucopenia or increased liver enzymes.

There is some literature to support the use of this drug in pediatrics, but it’s really only recommended in those where nothing else is working for their disease or the way that the guidelines state it is in those where there is significant psychosocial impact on the family unit. Definitely not a first-line option that we would recommend with regard to our systemic agents.

The last one that we focus on is cyclosporine, again an older drug, an immunosuppressant that’s used for numerous disease states. But it does have studies showing its efficacy in atopic dermatitis. Some of the side effects to think about with this medication are going to be neurotoxicity. The lesser ones— headache, hypertension, tremor, gingival hyperplasia can be one of those rare adverse effects that we can see with cyclosporine. And there have been reports of increased skin cancer.

Peter Lio, MD: Thank you. Of course, all of those agents are off label for atopic dermatitis in the United States. Cyclosporine is on-label in Europe in certain situations for adults, but that’s made it tough because sometimes we try to write for these things and we get rejected because they say, wait a minute, you’re being off label.

This transcript has been edited for clarity.