Seminal research led by Emma Guttman-Yassky, MD, Associate Professor of Dermatology, and Medicine (Clinical Immunology), at Icahn School of Medicine at Mount Sinai, has identified the key drivers of eczema and given rise to promising new treatments that appear to reverse the disease.
Dr. Guttman-Yassky and her team of researchers at Mount Sinai were the first to locate the activated pathways in eczema, or atopic dermatitis, specifically the Th2 pathway (driven by IL-4 and IL-13 cytokines) and the Th22 pathway (driven by the IL-22 cytokine). They found that these cytokines, or immune proteins, are responsible for the inflammatory, red, and extremely pruritic rashes that characterize eczema, as well as the defective epidermal barrier that allows increased penetration of allergens, irritants, bacteria, and viruses.
In a phase 1b clinical trial that was coupled with mechanistic studies performed by Dr. Guttman-Yassky’s group at Mount Sinai and researchers at Rockefeller University, the scientists found that dupilumab, a novel drug from Regeneron Pharmaceuticals Inc., effectively reversed the disease both clinically and in tissues. This trial and the phase II studies were so successful that the U.S. Food and Drug Administration fast-tracked development of dupilumab, which could be available as soon as 2017.
The results of this trial—conducted in collaboration with Regeneron, Sanofi, and researchers from Rockefeller University—were published in the December 2014 issue of The Journal of Allergy and Clinical Immunology.
“This drug is a game changer,” says Dr. Guttman-Yassky, also the Director of the Center of Excellence in Eczema at The Mount Sinai Hospital. “It brings hope to patients with eczema who have tried everything. This disease is very debilitating. People cannot work and cannot sleep because of extreme itching. For many people, their whole lives are affected. It’s extremely gratifying for me to be able to help them.”
Backed by a $2.7 million grant from the National Institutes of Health, Dr. Guttman-Yassky is currently recruiting patients for another clinical trial she is leading that will test a drug made by Pfizer Inc. that targets the Th22 pathway (targeting the cytokine IL-22), which she also identified as activated in eczema.
“This is a profound change in the way we treat atopic dermatitis,” says Mark Lebwohl, MD, Sol and Clara Kest Professor of Dermatology and Chair of the Kimberly and Eric J. Waldman Department of Dermatology at Icahn School of Medicine at Mount Sinai. “Dr. Guttman-Yassky has given us a way to treat this awful disease with biologic agents, which is likely to be much safer than any treatment we’ve used in the past.”
According to the National Institutes of Health, an estimated 31 million adults and children in the United States have eczema. The number may actually be higher, but many people with the disease are never diagnosed by a physician.
Current treatments for moderate-to-severe atopic dermatitis include the drugs prednisone and cyclosporine, as well as phototherapy. All have drawbacks, however. The drugs target the entire immune system and can cause severe side effects, while phototherapy requires the patient to visit a doctor three times weekly.