Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University Health Sciences Center, explains current knowledge on the pathology of atopic dermatitis and use of targeted biologic therapies.
Atopic dermatitis (AD) is a systemic, type 2 immune dysfunction disorder, and its pathology has led to the development of several effective targeted biologic therapies, said Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University Health Sciences Center.
Can you describe current knowledge on AD and what investigative targets warrant consideration?
So, AD isn't a single disease, it's a phenotype. And it's becoming increasingly clear that it's part of a larger systemic, type 2 immune dysfunction disorder—classically or historically, what's been described as the atopic march, and that's an atopy or atopic condition that starts in infancy. It starts under age 2 in 80% of the patients, and mostly it starts with skin disease. And about 30% of kids who have skin disease have food allergies.
Then as time goes on, and particularly for the subset of patients who have uncontrolled skin disease, or more severe skin disease, they'll go on and develop other atopic morbidities. Usually, beginning with allergic rhinitis, and then sometimes conjunctivitis and asthma can develop, and then a smaller subset of kids have eosinophilic gut disease.
We now know, because we've had the great benefit of having some targeted biologic therapy, and having targeted biologic therapy is really what helps to support the immunologic basis of this disease—when you can really target a pathway that has been defined through a whole variety of other types of in vivo and in vitro studies as being the abnormal pathway.
So now we have some very narrow targeted biologics, beginning with the blocking of interleukin (IL)-4, IL-13 alpha receptor, and it has had incredible benefit in treating atopic diseases, not just AD, but also FDA approved for asthma, and in clinical trials for chronic rhinosinusitis with polyposis in adults. There's a variety of other atopic disorders that are also in clinical trials right now to benefit from using that specific targeted biologic therapy.
There's a number of other biologics in the same pathway that are currently under investigation—just looking at targeting IL-13 ligand, as well as IL-13 receptor moiety, and then other biologics as well. Some have failed—so targeting IL-31, for example, is much more effective at targeting itch, but less effective at curing eczema. And then clinical trials in adults for thymic stromal lymphopoietin, which was a promising molecule that looked like, at least genetically, it played a big role in AD, but didn't seem to work in clinical trials in adults.
There's also broader immunosuppressive targets that work in this spectrum of disease. So, historically methotrexate and cyclosporine, and then more recently, a whole variety of selective and nonselective Janus kinase (JAK) inhibitors have been shown to improve this kind of inflammation for patients.