AD Management With Immunosuppressants

Elaine Siegfried, MD: All systemic treatments for atopic dermatitis, except for the newest one, are used off-label. And we’ve used those because we had nothing else to use. We had patients who were suffering so we turned to what I call the Big Guns, the systemic immunosuppressant medications. There are 4 of them—methotrexate, cyclosporine, azathioprine, and mycophenolate—that have been standard, used for just habit reasons. People don’t use some of the other immunosuppressants like tacrolimus. That one probably doesn’t work as well systemically, although it’s used topically. And it has a lot of adverse effects.

So we use those in adolescents and they’re used in adults. They’re just difficult to use and they have a lot of adverse effects. My favorite one is methotrexate though. Methotrexate is not so difficult to use. You take it once a week but it’s a little bit difficult to adjust. It’s got a very slow onset. The dose is not well worked out. It requires laboratory monitoring, and the parameters for even monitoring methotrexate are not uniformly accepted. But it’s used for so many diseases by different specialties—GI [gastrointestinal], rheumatology, hematology-oncology, allergy immunology, and now dermatology. So we use a lot of methotrexate but we have a lot of unknowns.

We are sponsored by the Pediatric Dermatology Research Alliance. We have a big consortium that we’re working on now for uniform guidelines for use of methotrexate for all kinds of inflammatory skin diseases. But it’s a mainstay of treatment for atopic dermatitis, and it’s a good treatment. But in adolescents, for females of childbearing years, it’s abortifacient and a teratogen. So once you get to be that age and you’ve been on methotrexate for a while, it’s time to get off.

Julie Block: The use of systemic therapies for children with atopic dermatitis is receiving a lot more attention. What we know now, and we’ve known for a long time, this is part of the education we spoke of earlier about what needs to be known about systemic therapies. The ones that are used for children are all used off-label, except prednisone. And we also know systemic prednisone is a very risky drug for children and adults. There are many risks with those systemic therapies. They need to be used with extreme caution, and now we know we have a newcomer to the market, a new biologic that we are very hopeful is a safer drug. And we also know that the ongoing studies and the value of the biologic have received great acclaim so far. So we are thrilled and very excited about that.

One of the greatest questions we get at the National Eczema Association from moms and dads when their topicals fail and they’re at their wits’ end, and they want to know is what do they turn to next, we talk about the current systemic therapies. And they are very surprised to learn that 1) they’re not indicated for atopic dermatitis, and that they come with the risks that they do. So they can be effective, and they can be used in the short term. I don’t think they are seen as a long-term solution for moderate to severe atopic dermatitis.

Elaine Siegfried, MD: Regarding adverse effects of the immune suppressants that are used for atopic dermatitis, methotrexate is really the most well tolerated. There are well known adverse effects, and liver toxicity is one of them, although liver toxicity is probably related to other risk factors. So in adults, and particularly adults with psoriasis, which is the disease where methotrexate has been used historically a lot, they tend to be overweight, and they drink. And those are big risk factors for liver problems. And so in that population methotrexate is a lot harder to use. Children really don’t have those risk factors, and particularly children with atopic dermatitis—they tend to be thinner rather than bigger. And so that’s 1 of the reasons that methotrexate is a great drug for that population.

A small percentage of kids get sort of queasy and they get nauseated, and sometimes they’ll have some lab abnormalities, low white count or a little bit elevated liver tests. Those may or may not actually be related to the methotrexate, and you can really mitigate the nausea if you just take supplemental folic acid. So methotrexate’s really well tolerated. It’s a cheap drug. It works well, but it’s not FDA approved for this condition. And we would like it to be. We would like to use it as an active comparator for trials of new medications, but that’s never going to happen for those kind of medical legal reasons that it’s not FDA approved. And a lot of people are hesitant to use methotrexate just for that reason.

People are also kind of frightened of methotrexate because it’s used in very high doses—300 times the dose that we use for atopic dermatitis for children who have leukemia. It’s a miracle for those children, part of their reason that that’s got such a high cure rate now. But it’s scary for people to think about using a drug like that.

Cyclosporine is the next most common one, and I use a fair amount of cyclosporine. Cyclosporine is a drug that you can use to kind of put out the fire because it’s a pretty strong drug, and it’s got a quick onset as opposed to methotrexate, which takes about 3 months to kick in.

So cyclosporine works pretty quickly but it has kidney toxicity, and it requires blood test monitoring pretty much every month. Like methotrexate you can get away with not doing blood tests quite as often, but cyclosporine you have to do blood testing. And you want to use it for short term because long term it’s got a lot of adverse effects, including immunosuppression, that you just don’t want to take that risk for a disease like atopic dermatitis.

And the other 2—azathioprine, mycophenolate—I’ve treated children with that in years past, but I haven’t used them for years because they just don’t work that well and they’re much harder to use. And they also had immune suppression, particularly azathioprine, which has been associated with hepatic cancer, particularly in boys who have been treated for Crohn disease, so it’s a little scary.