Mount Sinai researcher explores keloid response to Dupixent

Emma Guttman-Yassky

Preliminary findings from Emma Guttman-Yassky, MD, PhD, and colleagues demonstrate a novel use of dupilumab for managing chronic keloids with reductions in skin fibrosis and keloidal scarring, which may suggest a potential underlying Th2 pathogenesis in keloid formation.

“This is really a paradigm change because when you think of keloids, people think they are an abnormal fibroblast growth, an abnormal wound healing. No one thinks it is an inflammatory condition. That’s completely a game changer,” Guttman-Yassky, of the department of dermatology and laboratory of inflammatory skin diseases at Icahn School of Medicine at Mount Sinai, told Healio. “No one thought of immune molecules being increased in keloids or that you can target keloids with an immune-targeted treatment.”

Her discovery began with an African American patient with moderate to severe atopic dermatitis (AD) who also had two keloids, one medium and one large. Guttman-Yassky biopsied the keloids and found no skin cancer.

“I was not thinking of his keloids, but I gave him 300 mg dupilumab (Dupixent, Sanofi/Regeneron) for his AD, given every 2 weeks. He came back in 6 to 7 months after treatment and was very happy,” Guttman-Yassky said. “I was thinking he was pleased because the eczema improved, which it did. But he was so happy because one keloid disappeared completely and the other was largely gone. His pain and itching also resolved.”

Seven months after treatment with dupilumab, the patient had significant AD improvement, with Body Surface Area of 8%, SCORing Atopic Dermatitis of 16 and Eczema Area and Severity Index of 10 compared with baseline scores of BSA 70%, SCORAD 50 and EASI 33.

Guttman-Yassky found shrinkage of the large keloid, flattening of the surrounding borders and complete disappearance of the smaller keloid, according to a research letter in Journal of the European Academy of Dermatology and Venereology.

Guttman-Yassky and colleagues then explored the T helper 2 (Th2) gene expression in lesional and nonlesional keloid skin among three previously reported African American patients with severe chronic keloids with no concurrent atopic dermatitis and five healthy African American control patients.

Interleukin-4R, which dupilumab targets, was highly upregulated in keloid lesions compared with control patients, according to the paper. A key Th2 cytokine, IL-13, was significantly increased in lesional and nonlesional keloids compared with controls (P < .05). Additionally, Guttman-Yassky and colleagues found an increase in the Th2 chemokine, CCL18, in keloids, particularly in nonlesional skin (P < .05).

“Now, I see more and more patients with keloids. I am amazed about the level to which they suffer,” she said. “They have intense pain and itching in these lesions. They want the keloids to shrink, but they also want the pain and itching to go away.”

The current gold standard management is surgery and radiation, she said. Keloids can be debilitating, and African Americans will often have resulting keloids after any surgery or significant trauma.

A large upcoming study may begin as soon as early 2020 to explore the effectiveness of dupilumab on keloids, perhaps at a weekly dose, as patients with keloids tend to be “very inflammatory,” she said.

“When you look at patients with keloids, many will have allergy of some type in their background or within their family,” she said. “We are contemplating having at least 50% of the patients in the study with an allergy of some sort. It appears that when you have a patient with keloids, there is also a very strong allergy background present.”

This discovery may lead to the potential for minimizing keloids by providing noninvasive treatment targeting the Th-2 pathway.

“It changes the whole paradigm in making these keloids immune-driven similar to atopic dermatitis,” Guttman-Yassky said. – by Abigail Sutton

Reference:

Guttman-Yassky E, et al. J Eur Acad Dermatol Venereol. 2019;doi:10.1111/jdv.16097.

Disclosures: Guttman-Yassky has received research funds from AbbVie, Almirall, AnaptysBio, Asana, Boehringer-Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly, Glenmark, Galderma, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Regeneron, Ralexar, Sienna Biopharm, Union and UCB; and consults for AbbVie, Amgen, Asana Biosciences, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Fix Bio, Galderma, Glenmark, Incyte, Kyowa, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi Aventis, Sienna Biopharm and Union Therapeutics. Please see the study for all other authors’ relevant financial disclosures.