VIDEO: Exploring biologics, JAK inhibitors, other treatment options in atopic dermatitis

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Sure is a lot longer list than it used to be. I will start there. As far as mild disease, sometimes it can be as simple as just good skincare, moisturizing, especially after baths, avoiding irritants, avoiding allergens, realizing that atopic dermatitis can flare with the seasons, so being mindful of those sorts of changes that you might need to flex with, but generally, just taking good care of your skin.

Once you get to the more mild to moderate end of the spectrum, then you might need to involve prescription medications, and the time-honored treatment that we still use quite frequently are topical steroids. They have their pros and cons of course, but for most, they work well and can be used safely and sustainably. When topical steroids are either not as sufficiently effective as you might like or you're concerned about overuse and you're still in that mild to moderate end of the spectrum, we do have prescription non-steroidal options. The ones that have been around the longest are the topical calcineurin inhibitors, pimecrolimus cream, tacrolimus ointment, approved in the U.S. older than the age of two. We used those quite frequently. There was a newer non-steroidal agent approved in 2017 called crisaborole, which is approved down to three months of age for mild to moderate atopic dermatitis, and then just recently, a couple new non-steroidals approved. So that's the sort of range of things we generally do for mild to moderate.

When we get into more severe into the spectrum, that's where we've made the biggest leaps in the last few years with new biologic medications, new small molecule medications, and a pipeline that is replete. Yes, maybe the best way to contextualize that is I finished my fellowship in the year 2000, and from 2000-2001 to 2017, there were no new molecules approved for atopic dermatitis. Since 2017, there've been, gosh, getting hard to count now, certainly more than six, so quite a change.

Topically, I alluded to those a little bit earlier, the non-steroidal tapinarof is a topical non-steroidal, approved down to two years of age, once a day use. Many of the things we've historically used topically have been twice a day. Some of the newer treatments are indicated for once a day use, which is certainly convenience and a step forward for parents and patients. And then there's a medication called roflumilast. I'm using all nongeneric names of these medications. Roflumilast is also a topical nonsteroidal, so phosphodiesterase inhibitor, which is approved now to six years of age for once a day use for mild to moderate atopic dermatitis.

So topically, yes, systemically, my goodness, 2017, that sort of benchmark date I alluded to earlier, was when dupilumab was approved. It's a biologic medication, injectable medication, depending on your age, once a month or every two weeks. It was initially approved in 2017 for adults, and then seemingly every year, that age of approval has gone down to the point now where it is FDA approved for moderate to severe atopic dermatitis down to six months of age, which is truly remarkable. We also have two other medications, now three, actually, biologic medications, two that are somewhat similar in mechanism too, the dupilumab, one called tralokinumab, which is an IL-13 blocker, and lebrikizumab, the most recently approved one of this sort, also an IL-13 blocker. And then nemolizumab, an IL-31, different target, IL-31 is oftentimes called the itch cytokine, so this is a biologic molecule that blocks IL-31. Approved, these latter few I've mentioned, dupilumab down to six months of age, tralokinumab, lebrikizumab, nemolizumab, down to 12 years of age, so a little bit different age of approval, at least presently.

And then we've got small molecules, JAK inhibitors specifically, two have been approved in the United States by the FDA, upadacitinib, a once a day pill for moderate to severe atopic dermatitis down to 12 years of age, and abrocitinib, also an oral JAK inhibitor, approved down to 12 years of age. In Europe, there is an oral JAK inhibitor called Bbricitinib, which is approved by the EMA for atopic dermatitis, moderate to severe, but approved in the United States for alopecia areata, but not atopic dermatitis.

So long list, I hope I'm not forgetting any of the new ones. It's a nice problem to have that I'm actually worried I might be omitting one.

That many more options, the landscape has changed for sure. And I guess one of the biggest things is we've, gosh, prior to 2000 for sure, and even still, we rely heavily on topical steroids, and topical steroids are effective and can be used safely and sustainably, but they can have side effects, but they also have baggage well beyond their side effects. Parents do not like putting them on, do not like using them, and so it's a real struggle. So I think the landscape in that sense, very fundamentally has changed in that we have other options.

You know, we have the Hippocratic Oath, right? First do no harm. Parents are the original Hippocratic Oathers, right? They really don't wanna do harm to their child, and so they also live with their child. We're talking on the moderate to severe end of the spectrum, children losing sleep every night, itching constantly, not able to focus in school. This is incredibly impactful disease on that end of the spectrum, and so they also see the harm of not treating. And so it's a real catch 22 for many parents when you have a treatment that is recommended that they have qualms about. So it's lovely to be able to now have a wider pallette of options to offer, and as we've talked about, there's a genetic basis for this disease, that filaggrin molecule.

So oftentimes their parents themselves have dealt with this when they were little, and it's always interesting to see when we start laying out the options now, they're very eyeopening because it's so, so very different than the options they were given when they were children. Other question that is asked and not yet fully answered is, and this spans to other disease states in dermatology as well, psoriasis for instance, if we intervene early, can we actually prevent the development of comorbidities down the line?

So atopic dermatitis, we've always talked about the atopic triad or the atopic march, food allergies and eczema as a baby, asthma as a child, hay fever as an adult. Some kids march orderly through all three, some get one or the other, but certainly they are tightly linked. And now we have seen just an incredible array of additional comorbidities that are seemingly very, not just associations, actually truly linked either genetically or possibly causally with atopic dermatitis like alopecia areata, urticaria, mental health aspects linked as well, so a whole lot of things that can sort of stem from atopic dermatitis as a young child. And the question then is if we were a little bit more effective and aggressive in managing it early, might we in fact prevent those comorbidities? And there was some early data saying just moisturizing the heck out of the skin of high-risk babies starting at three weeks of age can decrease the risk of developing atopic dermatitis, and then perhaps by extension other things. That's then there's some mixed literature with that, with regard to that specific question now, but just a fascinating line of investigation.