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Q&A: Dr Guttman on the Possibility of Dupilumab for Treating Keloids

Q&A: Dr Guttman on the Possibility of Dupilumab for Treating Keloids

Mon, 01/06/2020 - 15:20

Dr Guttman

Keloids can be frustrating for patients and dermatologists as there are few options that effectively treat them.

In a recent Letter to the Editor published in the Journal of the European Academy of Dermatology and Venereology, Aisleen Diaz et al1 showed improvements in 2 keloids on a patient with severe atopic dermatitis following treatment with dupilumab (Dupixent). The patient, a 53-year-old African American man, had one large and one medium-sized keloid in addition to post-inflammatory hypopigmentation and about 70% of his body surface area was affected by atopic dermatitis.

After 7 months of treatment, the patient experienced improvements in atopic dermatitis, with reductions to 8% of his body surface area affected. In addition, the smaller keloid completely resolved, and the larger keloid shrank by about 50%.

Following this surprising result, Diaz et al used real-time PCR to evaluate Th2 expression in keloid lesions from 3 previous African American patients and 5 healthy controls. They found the key Th2 cytokine, IL-13, was significantly increased in keloid skin compared with non-keloid skin.

Emma Guttman, MD, corresponding author of the study, discussed these findings with The Dermatologist. Dr Guttman is the Sol and Clara Kest Professor and vice chair for research at the department of dermatology, director of the Center for Excellence in Eczema, and director of the Laboratory of Inflammatory Skin Diseases at the Ichan School of Medicine at Mount Sinai Medical Center in New York, New York.

The Dermatologist: Could you briefly describe the study? Were you surprised to find dupilumab treatment improved your patient’s keloids?

Dr Guttman: I had an African American patient that had moderate to severe atopic dermatitis. He also had 2 keloids, one was really large and one I would say was medium sized. I was worried these keloids might have skin cancer so I biopsied them, but they were just keloids.

To treat his atopic dermatitis, I put him on dupilumab. The patient came back about 6 to 7 months later super happy. I thought he was happy because his atopic dermatitis was going away, but he said that in addition to his atopic dermatitis going away one of his keloids completely went away. And, I looked at the other one and it had shrunk by 50%. I was surprised because this was not known before.

The Dermatologist: What mechanisms did you identify that explain why dupilumab was effective for this patient’s keloids?

Dr Guttman: In collaboration with other colleagues, we obtained 3 lesional keloids and 3 non-lesional keloids and assessed the profile of these lesions. We saw that the molecules that dupilumab targets, IL-4 receptor and IL-13, as well as a few others in the same pathway, were activated in keloids. We still are investigating, but we do believe that IL-4 and IL-13 have major effects on fibrosis, which is probably why the IL-4 receptor blocker was effective here.

Prior to this particular case, nobody considered that keloids are immune-driven or that immune molecules were involved in keloids. Mostly it was thought that keloids were primarily an abnormal wound healing response. We are definitely doing more investigation into this, but I think this opens the door to novel treatments and shows keloids can be treated with immune-targeted therapies.

The Dermatologist: At this time, do you know if this discovery will also help in the identification of atopic dermatitis phenotypes?

Dr Guttmen: I think it will help us understand atopic dermatitis as well because patients with AD have increased thickening of the skin. Understanding keloids may help us understand the process of lichenification in AD, and vice versa.

The Dermatologist: How will this revolutionize the treatment of keloids and what research is needed to confirm the findings from your study?

Dr Guttman: We are very excited because patients currently have no treatment option that is 100% effective. The gold standard for keloids is surgery or radiation, which have high recurrence rates.

We are in the process of initiating a much larger, appropriate trial to investigate the use of dupilumab as a treatment for patients with keloids. In the study, we will administer a higher dose of subcutaneous dupilumab once a week because we believe a much higher dose is needed to treat keloids compared with atopic dermatitis.

Also, it is clear there is crosstalk between fibroblasts and other immune molecules in the setting of keloids but we need to better understand how these fibroblasts are related to the immune molecules.

I think it is a very exciting time for patients with keloids because we might be able to offer them a paradigm changing treatment in the future.

Reference

1. Diaz A, Tan K, He H, et a. Keloid lesions show increased IL-4/IL-13 signaling and respond to Th2-targeting dupilumab therapy [published online November 20, 2019]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.16097

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