Interview With Jonathan Silverberg, MD, PhD, MPH: Clinical Considerations in Treatment Selection for Atopic Dermatitis

So, I'm in an academic setting. I see [patients] as a board certified dermatologist. We're an academic referral center and I get a lot of atopic dermatitis, a lot of contact dermatitis, itch, chronic inflammatory skin disease. I tend to see some more challenging cases that have already been seen by other astute dermatologists out in private practice. [I've] had the privilege of being on the cutting edge in this field for a while and getting to see the arrival of some pretty cool new therapies. With respect to clinical trials, I've actually been engaged in clinical trials for atopic dermatitis for...over a decade now. Some of the earliest trials for atopic dermatitis that I participated in were the original phase 1 dupilumab studies for atopic dermatitis, as well as the clinical trials for probably every single new agent that we have approved now or in late stage coming for atopic dermatitis. So it's been a very exciting time in the field for clinical trials.

Atopic dermatitis [is] a complicated disease. It's a heterogeneous one with activation of a number of immune pathways. We think very highly of the role of interleukin(IL)-13 and interleukin-4, the broader TL-2 pathway. But there are certainly other cytokines that play a very important role, like interleukin-31. There may be subsets of patients where interleukin-22 plays a role and perhaps other cytokines as well. So when we think about the possible overlaps, there are several nodes or points where those overlaps may occur. There are certainly a number of other TLP-2 mediated diseases in the immune spectrum particularly within allergic or atopic disease such as asthma, hay fever, food allergies, eosinophilic esophagitis, etc. We're learning more and more every day. On the IL-31 side of things we know that it's a very important role for IL-31 in prurigo nodularis, but there are now growing discussions about the role of IL-31, potentially even in disorders like scleroderma and urticaria potentially. And I think that's very early days, so we have a lot to learn. We know a lot less about the role of interleukin-22, so that's an area that I think we still need a lot more research. Thymic stromal lymphopoietin has been implicated in atopic dermatitis as well. [That one] also has an important role in asthma. A number of different potential areas of overlap. Some of them are more theoretical, some of them are more practical in the sense that for example, let's say with prurigo nodularis, I'm of the mindset that prurigo nodularis is really a standalone disorder and a separate diagnosis from atopic dermatitis. That said, some atopic dermatitis patients can actually manifest with prurigo nodules. Sometimes we see those overlaps actually happening in the same patient, and other times it's more of a higher level mechanistic overlap of disease.

The last guideline update we had for atopic dermatitis was about a decade ago. A lot has changed...in the field. Those last guidelines were developed prior to the approval of dupilumab and crisaborole, which were the first of the innovations in atopic dermatitis. Since then we've had multiple biologics, multiple other topicals in development, multiple orals, and none of that was reflected in the guidelines. If you were to just consult with the older guidelines, your conclusion would be use cyclosporine with a weak body of evidence. So it really was very outdated and needed to be brought up to date with all of the innovation. I would argue [it will] soon need to be updated again because of all that is rapidly evolving in the field. It was a necessary update. [And it's a] 4-part guideline update. So we've got the update on comorbidities. We've got the update on topical therapies, and we've got the update now on systemic and biologics. Then the fourth and last part, which will be coming very soon, is the update on particularly pediatric atopic dermatitis, which has its own special considerations.

We have now an extraordinary body of evidence from real world studies in support of the real world effectiveness and safety of dupilumab for atopic dermatitis and other indications as well. You almost can't go a single month, for some of the dermatology [and] allergy journals, where you don't see a real world study examining dupilumab in different clinical scenarios. But we have studies now…reproducing, essentially, very good…results…seen efficacy-wise in clinical trials showing that there’s good clinical effectiveness in the real world. We've seen real world studies reproducing overall good safety profile in the real world. So I think we're quite comfortable based on the real world evidence that the results that were observed in the phase 3 studies are generalizable to our patients. But we've also seen studies examining a number of other endpoints that weren't as well studied in the clinical trials. For example, [there's] one study that looked at particularly dupilumab and its impact on sleep, showing major improvements in terms of a variety of different domains and aspects of sleep disturbance and sleep quality, etc. Improvements of dupilumab in terms of reducing hospitalization rates, decreasing comorbidity rates, reducing secondary infection rates studies that have looked at treatment persistence showing very good treatment persistence over time, which is sort of an aggregate measure indicating that there's both good effectiveness but also very good tolerability and safety so that patients are able to stay on the medications longer term. We've also seen studies that have shown very good improvements in terms of quality of life across a variety of different domains, school performance, work performance, cost-effectiveness. So, there's quite a bit of data out there showing that it's working really holistically across that whole atopic dermatitis patient.

For other articles and videos in this AJMC® Perspectives publication, please visit "Managing Atopic Dermatitis: Clinical Considerations, Payer Perspective, and 2024 Guidelines"