乌鸦传媒

Thinking of psoriasis and atopic dermatitis (AD) as a spectrum, rather than separate diseases, might lead to better understanding and potentially better treatments, two authors have proposed in .

"A case can be made that psoriasis and AD exist across a spectrum where polar T-cell axes can be variably present and create some overlapping disease characteristics," wrote Emma Guttman-Yassky, MD, PhD, of the Icahn School of Medicine at Mount Sinai Medical Center, and James G. Krueger, MD, PhD, of Rockefeller University, both in New York City.

When these T-cell mediated inflammatory skin diseases are studied in European-American populations, the differences between them are clear in both T-cell polarity and cytokine arrays, they noted.

Psoriasis is driven in large part by Th17 T-cells and the associated activation of IL-17, they said. In contrast, a strong driver of AD is T乌鸦传媒, which is associated with overproduction of IL-4 and IL-13.

However, subtypes, including Asian-origin, pediatric, and intrinsic AD have a prominent IL-17 component. That, along with tissue patterning that overlaps with psoriasis histopathology, starts to build the case for a spectrum of immune disease, which is depicted graphically in the article.

"We used to think that atopic dermatitis was a purely T乌鸦传媒 disease," Guttman-Yassky said in an interview. "We now know that it's much more complex, and instead of being a homogeneous disease, it actually has different phenotypes. While T乌鸦传媒 activation is common to these phenotypes, they differ in activation of Th17 and T乌鸦传媒2 T-cell axes, which show for example significant increases in Asians with AD."

"So, we need to think about it as a continuum, and for different patient subsets with different phenotypes of atopic dermatitis, we need to think that maybe some treatments from the psoriasis arena may actually qualify," she added.

Where this mindset may be most useful now is in the development of targeted treatments, particularly for AD, the authors suggested. Targeting T乌鸦传媒 and IL-4/IL-13 with dupilumab (Dupixent) has proven to be a very effective strategy for atopic dermatitis.

However, the presence and influence of the Th17 cytokine axis in certain AD subtypes suggest treatment might be optimized by targeting multiple cytokines; in particular, targeting Th17/IL-23 has proven to be an effective treatment strategy for psoriasis, they noted.

Targeted treatment of AD is generally more complicated than that of psoriasis because multiple immune axes may contribute to AD disease pathogenesis, Guttman-Yassky said.

The approval of dupilumab for moderate-to-severe AD represented a major step forward in the targeted treatment of this disease, according to the authors. In particular, studies showed that approximately 60% of patients attained an EASI75 response on dupilumab, and 35% attain an EASI90 response.

However, studies of agents targeting IL-17, ixekizumab (Taltz) and brodalumab (Siliq), suggested PASI75 and PASI90 responses of 90% and 60%, respectively.

"We do not see these results in atopic dermatitis yet, even with very good drugs like dupilumab," Guttman-Yassky said in an interview. "So we may need to think that we need to target several axes in atopic dermatitis for complete disease resolution in AD because of differences between different cytokine axes in different AD phenotypes."

While the outcome of dupilumab treatment argues for a primary T乌鸦传媒-centered pathogenesis of AD, some investigations have shown that the drug also modulates the IL-23/Th17/T乌鸦传媒2 axes, the authors wrote.

As a result, it might be best to think about AD not only as a T乌鸦传媒-predominant disease, but as a "multi-axis" immune disease to which T乌鸦传媒2 and potentially Th17 are contributors; that would mean that combinations of targeted therapy could be required to achieve maximum therapeutic success, Guttman-Yassky and Krueger wrote.

In particular, T乌鸦传媒2 is also commonly present and activated across major AD subtypes, and clinical efficacy has been recently reported for the experimental anti-IL-22 antibody, fezakinumab, according to results of a 60-patient placebo controlled trial in the Journal of Investigative Dermatology.

Future studies need to determine whether subsets of patients, such as Asian AD patients, can benefit from targeted treatments that are effective in psoriasis, according to the authors. Also, the emergence of bi-specific and tri-specific antibodies could represent an opportunity to improve on single-cytokine targeting approaches in this disease.

"Psoriasis is about 10 years, if not 12 years, ahead of atopic dermatitis" in development of targeted therapeutics, Guttman-Yassky said in the interview. "I think we'll need to still have single targeting in atopic dermatitis with all these agents to really understand their contribution for the disease. And then we may need to also think about dual targeting to really achieve maximum disease control."

This article originally appeared on our partner's website , which is a part of UBM Medica. (Free registration is required.)

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