Pharmacological treatment options for atopic dermatitis

Raj J. Chovatiya, MD, PhD: That brings me to some of these treatment goals that we think of when it comes to atopic dermatitis? As Lisa so aptly pointed out with shared decision making, each patient and each family will have different goals and values. Generally speaking, there are universal things that people are looking for. When it comes to treatment, people want something that works, short term and long term. Not something that is going to be a temporary fix. Something that will continue to work, not just one day all of a sudden, oops, it stops, and the atopic dermatitis comes back. Something that makes them feel safe, that they can continue to use it. A bigger one that we don’t talk about is something they can access and get their hands on. So if there’s a good therapy, they can use it, and it’s not something theoretical that they can use.

When I think about patient factors in regards to treatment options, just like Lisa said, I like to explain everything to my patients. Perhaps some might consider this to be over-information. I consider this an empowerment. Because you’ll never really know what the best treatment is for someone unless you talk to them about your options. 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 aren’t always the most achievable for patients. I would much rather have something in place that I know someone can follow and a family will follow, than something that is either too complicated, too hard to get, or too expensive, and there are a lot of Other daily patient factors you want to think about when it comes to this therapy.

In terms of the state of the art in treatment, we kind of hinted at what this step therapy looks like, this diagram. The only additional thing I could add is that we are still thinking about scaling up therapy. There is significant power in stepping up and stepping down. In short, do not complicate the lives of our patients too much. We are all guilty of it by saying, “Here is another cream. Here is another ointment. Here is another cream. Pretty soon you come up with a whole bag of stuff saying, “I don’t know exactly what I’m supposed to use.” On a daily basis, I barely remember to hydrate myself, and that’s just one thing. I can only imagine how difficult it is if you have something for your face, something for your hands, something for your body, something for Tuesdays, something for Saturdays. A lot of our power is trying to figure out how we can make plans that almost eliminate an iatrogenic burden, that’s the word I would use, where I’m not making your life harder, but something that will work. We highlighted topical therapy as an important step for people with mild to moderate disease. Topicals generally work by reducing inflammation. In the case of emollients, they help repair the skin barrier.

Topical corticosteroids are the most commonly used. They range from low power to high power. They come in various forms, there are creams, ointments, lotions, oils, solutions, foams, for different parts of the body. This is usually the first place where most patients with atopic dermatitis start. Now, for many people, topical corticosteroids are an excellent choice. They’re pretty cheap, easy to get to, and can work really well. But you may experience problems with topical corticosteroids. Sometimes they stop working for patients. Sometimes you need to use a stronger agent, but you are limited based on a few factors. Usually in areas of thin and sensitive skin you can’t use some of the strongest therapies we have. We encounter problems with thinning of the skin, loss of fat under the skin, even pigmentation problems on the skin. When it comes to the face, body folds, and genitals, those kinds of areas, there are huge limitations to the therapy we have. Also, with chronic use of topical corticosteroids or any other topical product, there are small levels of absorption from whatever you use. You can imagine that years of topical corticosteroid use could also lead to other issues when it comes to chronic steroid therapy use.

There are other topical therapies that Lisa has discussed. We have calcineurin inhibitors, phosphodiesterase-4 inhibitors, and then a new JAK inhibitor as well. These all work by specifically targeting different molecules. So where topical corticosteroids act a bit more broadly, generally reducing inflammatory activity, topical calcineurin inhibitors are a bit more specific. They still act very broadly, but they are non-steroidal. They eliminate some of the problems I mentioned with topical corticosteroids. The downside is that they can usually be associated with stinging and burning, especially in areas of sensitive skin, and there are only a few options, tacrolimus and pimecrolimus, both of which have limited effectiveness . Sometimes you won’t get the boost you need from these medications.

There is a phosphodiesterase-4 inhibitor on the market, this is a specific molecule that inhibits an overactive skin enzyme in atopic dermatitis. Crisaborole, that’s what it’s called. Again, this one is probably potency limited overall, and this one probably has the highest rates of skin symptoms in terms of stinging, burning, and itching. It’s not exactly the easiest therapy for patients to use. A newer one, approved for ages 12 and older, is topical ruxolitinib. This is called a JAK inhibitor. In broad terms, it is a specific targeted therapy that acts on a class of proteins that are overactive in atopic dermatitis and involved in many different signaling pathways that relate to both what passes on the skin and to symptoms such as itching. . This one has good power. It is not a steroid so you don’t have to worry about some of the steroid side effects. There are other issues to deal with. This whole family of drugs, JAK inhibitors, contains a boxed warning, which is another important part of this shared decision-making discussion, based on long-term studies with older oral drugs in this same class as well. There’s a bit more discussion about using this one to determine if it’s the right drug.

At this point, if topicals aren’t doing it for you, that’s when you start to move on to more advanced therapies in the moderate to severe range. Phototherapy is classic, narrow-band UV-B [ultraviolet B]-based therapy. It works well. It’s a bit cumbersome for patients to use, it’s a bit more historical in that sense. Typically, patients should come 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 skin inflammation. The downsides are that it is slow acting and again patients often have to physically go somewhere. Classically, we have used oral immunosuppressive therapy, so methotrexate is a classic treatment for atopic dermatitis. Cyclosporine is another, azathioprine is another. These are all drugs that have been the norm and still are in many other countries around the world. They work, not very well, but they work, but there are some drawbacks. You should monitor the results of lab tests. There are a whole host of potential blood, liver, kidney issues that you need to watch out for. For people with bad disease, that’s what we’ve had to deal with for years.

Transcript edited for clarity