Pharmacologic Treatment Options for Atopic Dermatitis

Raj J. Chovatiya, MD, PhD: That brings me to talking about what are some of those goals for therapy that we think about when it comes to atopic dermatitis? As Lisa so beautifully highlighted with shared decision-making, there are different goals and values that every patient and family is going to have. Generally speaking, there are some universal things that people are looking for. When it comes to treatment, individuals want something that’s going to work, both in the short term and the long term. Not something that’s going to be a temporary fix. Something that’s going to keep working, not that one day suddenly, oops, it stops, and the atopic dermatitis comes back. Something that makes them feel safe, that they can keep using it. A bigger one that we don’t talk about is something they can access and get their hands on. So if there is a great therapy, they can use it, and it’s not some theoretical thing that they can use.

When I’m thinking about patient factors when it comes to treatment options, very much as Lisa said, I love to lay it all out for my patients. Perhaps some might view it as over-information. I view it as empowerment. Because you’re never really going to know what is the best treatment for someone unless you talk to them about the options that are out there. You may have an idea in your mind of what you think you want to do, but at the end of the day, the best plans are not always the most feasible for patients. I would much rather have something in place that I know somebody’s going to be able to follow and a family’s going to follow through, than something that is either too complicated, too hard to get, is too expensive, and there are a lot of other patient day-to-day factors you want to think about when it comes to that therapy.

In terms of the state of the art as far as treatment goes, we alluded a bit to what that stepwise therapy, that diagram, looks like. The one extra element I might add is we always think about stepping up therapy. There's important power in stepping up and stepping down. Basically, not complicating the life of our patients too much. We’re all guilty of it, saying, “Here’s another cream. Here’s another ointment. Here’s another cream.” Pretty soon you come in with an entire bag of stuff being like, “I’m not exactly sure what I’m supposed to use.” On a day-to-day basis, I can barely remember to moisturize myself, and that’s just one thing. I could only imagine how difficult is if you have something for the face, something for your hands, something for the body, something for Tuesdays, something for Saturdays. A lot of our power is trying to figure out how we can make plans that almost remove an iatrogenic burden is the word I would use, where I’m not making your life too complicated, but something that’s going to work. We highlighted topical therapy as an important step for people with mild to moderate disease. Topicals typically work by reducing inflammation. In the case of emollients, they help with barrier repair on the skin.

Topical corticosteroids are the most commonly used. They range from low potency all the way to high potency. They come in a variety of forms, there are creams, ointments, lotions, oils, solutions, foams, for different parts of the body. This is usually the first place that most patients with atopic dermatitis start. Now, for a lot of folks, topical corticosteroids are a great choice. They’re pretty cheap, easy to access, and they can work really well. But you can run into issues with topical corticosteroids. Sometimes, they stop working for patients. Sometimes you need to use a more potent agent, but you’re limited based on a couple of factors. Usually in areas of thin and sensitive skin, you can’t use some of the strongest therapies we have. We run into problems of skin thinning, loss of fat under the skin, even pigmentary problems on the skin. When it comes to the face, and body folds, and genitals, these kinds of areas, there are huge limitations on what therapy we have. Additionally, with chronic use of topical corticosteroids or any topical, there are some small levels of absorption of anything that you’re using. You could imagine that years of use of topical corticosteroids could also lead to other issues down the road as it relates to just chronic use of steroid-based therapies.

There are other topical therapies that Lisa touched on. We have calcineurin inhibitors, phosphodiesterase-4 inhibitors, and then a newer JAK inhibitor as well. These all work by specifically targeting different molecules. So where topical corticosteroids are a little more broadly acting, they generally reduce inflammatory activity, topical calcineurin inhibitors are a little more specific. Still very broadly acting, but they’re nonsteroidal. They do eliminate some of the issues that I mentioned with topical corticosteroids. The downside there is that they can commonly be associated with stinging and burning, particularly in areas of sensitive skin, and there are only a couple of options, tacrolimus and pimecrolimus, both of which have limited efficacy. Sometimes you’re not going to get the boost that you need from these medications.

There’s one phosphodiesterase-4 inhibitor on the market, this is a specific molecule that inhibits one overactive enzyme in the skin in atopic dermatitis. Crisaborole is what that one’s called. Again, this one is probably overall limited by potency, and this one probably has the highest rates of cutaneous symptoms in terms of stinging and burning and itching. It’s not exactly the easiest therapy to use for patients. A newer one, approved for ages 12 and up, is topical ruxolitinib. This is what’s called a JAK inhibitor. In broad terms, this is a specific targeted therapy that works on a class of proteins that are overactive in the case of atopic dermatitis and involved in a lot of different signaling pathways that are related both to what’s going on to the skin and symptoms like itch. This one does have good potency. It isn’t a steroid, so you don't worry about some of the steroidal adverse effects. There are other issues to contend with. This entire family of medications, JAK inhibitors, do contain a boxed warning, which is another important part of that shared decision-making discussion, based on some long-term studies with older oral medications in that same class as well. There’s a little more discussion that goes into using this one to think about if it’s the right medication.

At that point, if topicals aren’t doing it for you, this is where you start stepping up to more advanced therapies in the moderate to severe range. Phototherapy is a classic one, narrowband UV-B [ultraviolet B]-based therapy. It works well. It is a bit cumbersome for patients to use, it’s a little more historical in that sense. Typically, patients have to go to the office at least 3 times a week, stand under a light box, and get a specific wavelength of light that can help reduce inflammation on the skin. The downsides are it’s slow acting, and again, patients often physically have to go somewhere. Classically, we’ve used oral immunosuppressive therapy, so methotrexate is a classic one for atopic dermatitis. Cyclosporine is another one, azathioprine is another. These are all medications that have been the standard, and still are in many other countries around the world. They work, not great, but they work, but there are some downsides. You have to monitor laboratory test results. There’s a whole host of potential issues related to blood, liver, kidneys, that you have to monitor. For people who have bad disease, these were what we had to contend with for years.

Transcript Edited for Clarity