Dr Elaine Siegfried Summarizes AD Treatment Guideline Update

In this interview, Elaine Siegfried, MD, of Saint Louis University School of Medicine, summarized the American Academy of Dermatology (AAD) guideline update published in November 2023 about treating atopic dermatitis (AD) using phototherapy and systemic therapies. She also gave her opinion on guidelines overall.

Siegfried diagnoses and treats skin-related disorders in infants and children; her specialties include AD, psoriasis, vascular birthmarks, and other eczemas. She is interested in research that investigates AD and pediatric drug development, as she participates in clinical trials for new eczema and psoriasis treatments. Siegfried is also a professor of pediatrics and dermatology in the Department of Pediatrics, Division of Dermatology, Saint Louis University School of Medicine.

Transcript

Could you please summarize the AAD's updated guideline recommendations for phototherapy and systemic therapies?

Just as by way of background, The last comprehensive guidelines were published in the Journal of the American Academy of Dermatology in 2014. Because so much has happened with this disease and new drug development for this spectrum of problems, the updated guidelines are much narrower just to try to bite off a smaller piece of that. So, the most recently published guidelines really focused on adults, and they focused on systemic treatments and phototherapy. The summary was very simple, and, just to put that into perspective, guidelines are something that requires broad consensus agreement and tries to look for evidence basis to support that agreement, but, just by virtue of the nature of trying to make guidelines, they're essentially really just oversimplified and are very difficult to draw generalized conclusions about how to manage any individual patient because individual patients are much more complicated than guidelines in general.

So, the one take-home message that I think there was in this publication was, in no uncertain terms, systemic corticosteroids are considered not a good treatment and even relatively contraindicated, even though that's one of the very few medications that's essentially FDA approved for this condition. That speaks to the issues related to FDA approval and restricting access to medications based on FDA approval and particularly restricting things like step edits based on what's historically been FDA approved.

Then, they also concentrated on phototherapy, talking about phototherapy in adults. It's an age old treatment, recommended narrowband UV-B as opposed to something like PUVA [psoralen plus UV-A], which has a little bit more risk and less well studied, but it really emphasized the fact that phototherapy is incredibly time consuming. While they didn't say this in the guidelines, and didn't address children at all, many people just can't afford the time; it requires 3 times a week and office visits for a minimum of 2 to 3 months. Then, after that, twice a week, and then, after that, long term.

They did talk about the the possibility of combining treatments, phototherapy and systemic treatments, or even more than one systemic treatment, which really speaks to the difficulty in treating this condition. Some cases are so severe that you can't really go by what's FDA approved or a single agent to keep the disease under control. So, they didn't say anything about children and phototherapy, but the time commitment is even harder for children who need to be in school and depend on parents for transportation, things like that.

Of the medications that they discussed, they recommended the FDA-approved ones with confidence, and that's strictly because we have level 1 prospective, double blind, placebo controlled trial data that support efficacy, and that's for adults. For children, it's a little bit different, and just so everyone knows, the number of children included in clinical trials to get that same kind of level 1 evidence is typically one-tenth the number of adults that are included in clinical trials, so much harder to have confidence, particularly in the safety data for such small number of patients and a unique subgroup of patients.

Although this guideline was focused on systemic treatment and phototherapy, they also mentioned topical medications that were available—topical corticosteroids, calcineurin inhibitors, pimecrolimus, tacrolimus, crisaborole ointment, and a PDE-4 [phosphodiesterase 4] inhibitor, and then a newer JAK [Janus kinase] inhibitor ruxolitinib cream. There are also some other topical medications that have been FDA approved since then that the guidelines does not include that are probably more promising than, and safer than, the ones that were mentioned.

In terms of the systemic therapies, they recommended with some confidence the FDA approved treatments dupilumab, that's been FDA approved and available since 2017, and tralokilumab, which was FDA approved I think about a year ago. There is another one that they didn't mention, lebrikizumab, that works through the same mechanism, which is very close to approval.

Then, they recommended 2 FDA-approved JAK inhibitors, upadacitinib and abrocitinib, and mentioned, without the higher level of recommendation because of the quality of the supportive evidence, the systemic treatments that have been used for many, many, many years—over 50 in the case of methotrexate, probably 30 or 40 for cyclosporine, azathioprine less so, and mycophenolate mofetil less so, but those are considered in this publication to be immunosuppressants. I don't consider methotrexate as much of an immunosuppressant as cyclosporine, azathioprine, and mycophenolate; it's more of an immunomodulating agent.

Then, it mentioned systemic corticosteroids. There was a strong recommendation against using systemic corticosteroids, and, I do have to say, through some claims database information that we have, that's still probably the number 1 systemic treatment that is still being used in this population, certainly inexpensive, but leads to all kinds of problems when used either repeatedly or long term.

So, that's the summary of those guidelines, and I have participated in guidelines, but I can't overemphasize that guidelines are an early starting point, and creating step edits and limiting access to medications based on published guidelines is not really what they were intended for and can really cause lots of problems for patients in delaying their access to appropriate personalized medication.