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Therapeutic drugs on the horizon in atopic dermatitis

NEW YORK — There are now multiple target treatments to utilize in patients with atopic dermatitis, but there is still a very large unmet need for better treatment in this disease, according to Emma Guttman-Yassky, MD, PhD, a Sol and Clara Kest professor of dermatology at Icahn School of Medicine at Mount Sinai in New York.

“Two years ago, I would summarize my lecture in 5 minutes, now I have difficulty determining what not to include in my 20-minute talk,” she said. “Many are not aware that atopic dermatitis is the most common inflammatory skin disease in the US, impacting 7% of adults and up to 25% of children worldwide, and 20% to 30% will have moderate to severe disease.”

“There is a very large unmet need for better treatment in this disease because we have only cyclosporine, phototherapy and immune suppressants for atopic dermatitis,” she said. “I want to convince you today that therapeutic drugs for this disease are finally imminent, but it wasn’t that simple,” she added.

“Is atopic dermatitis a homogeneous disease like psoriasis?” she asked the audience.

Most treatments are focused on IL-17 and IL-23 pathways. Atopic dermatitis is much more heterogeneous, with more clinical phenotypes like pediatric AD, African American AD, Asian AD and European-American AD, which affects differences in molecular phenotypes, Guttman-Yassky said.

Children have T helper 17 (Th17) activation, but Asians have a higher Th17 activation. Th1 is very different. African Americans don’t have any Th1 activation, whereas Europeans do in the chronic stage.

“All subtypes share robust Th2 activation and dupilumab (Dupixent; Regeneron, Sanofi Genzyme) targets Th2 and multiple other treatments. But Th2 is not the only game in town,” she added.

“We may need to target other axis in select patients. I think in atopic dermatitis there will be a role for personalized medicine in future years,” Guttman-Yassky added.

“All of us know about dupilumab, it is now approved in the U.S. in several indications and is a fully human multiclonal antibody. It targets IL-4 receptor alpha, so it targets IL-4 and IL-13 cytokine signaling,” she said.

Dupilumab is FDA approved for adolescents aged 12 years and older and is ongoing for approval in children aged 6 to 11 years. Surprisingly, less efficacy is seen in adolescents. “We know that adolescents don’t like to apply creams. Maybe there are differences in phenotypes that need to be considered,” she added. “We still see many adolescents clearing with this drug.”

Conjunctivitis is the only safety concern in most patients. “I see it in 5% to 10%, especially in those already exhibiting facial rashes,” she said.

Guttman-Yassky proposed another important question: Is IL-13 inhibition enough to control this disease? “For a while we did not have an answer, there were few proper studies about this.”

“IL-13 may be the most important cytokine that needs to be targeted as part of the Th2 oxys,” she said.

Next, Guttman-Yassky asked, “Can we reverse atopic dermatitis using strategies targeting the itch cytokine, IL-31?”

It is increased in AD lesions and associated with severity.

A phase 1 study of KHK4083 (Kyowa Hakko Kirin) demonstrated 80% lower EASI scores in patients with AD. “I think this is a very hopeful, potential new treatment that will happen in the future,” she said.

“Many companies are working on trials for drugs geared towards IL-33 targeting,” she said. – by Abigail Sutton

Reference:

Guttman-Yassky E. Hot topics in medical dermatology. Presented at: American Academy of Dermatology Summer Meeting 2019; July 25-28, New York.

Disclosures: Guttman-Yassky reports consultant or advisory roles with AbbVie, Allergan, Almirall, Amgen, Asana Biosciences, Celegene Corporation, Concert Pharmaceuticals, Dermavent sciences, Demira, DS Biopharma, Eli Lilly and company, EMD Serono, Escalier, FLX Bio, Galderma Research & Development, Glenmark Generics, Innovaderm Research, Janssen Pharmaceuticals, Kyowa Hakko Kirin Pharma, Leo Pharma, Medimmune, Mitsubishi Pharma, Novan, Novartis, Pfizer, Ralexar Therapeutics, Regeneron Pharmaceuticals, Sanofi/Aventis, Sanofi/Regeneron and Union Therapeutics.