Updates in Atopic Dermatitis

“The therapeutic drought is finally ending,” said Emma Guttman, MD, PhD, Sol and Clara Kest Professor of Dermatology and vice chair of the department of dermatology at Icahn School of Medicine at Mount Sinai in New York City, New York, during her presentation at the Interdisciplinary Autoimmune Summit 2020. She reviewed the latest therapeutic advances in the treatment of atopic dermatitis (AD).

There is debate in the literature on whether AD is barrier or immune driven, Dr Guttman explained. However, “we demonstrated in a paper that it does not matter where [AD] starts because what is perpetuating the disease phenotype through nonlinear stages are the immune abnormalities,” she said. She reviewed the pathogenetic cytokines in AD that are now being investigated as therapeutic targets, such as IL-13, IL-22, and IL-17.

Unlike psoriasis, AD is a more heterogeneous disease with multiple clinical phenotypes, stated Dr Guttman. There are biomarkers specific to different phenotypes in AD that may be important for developing a personalized medicine approach in the future. These biomarkers are being tested in clinical trials.

Dupilumab, an IL-4 receptor antagonist, revolutionized the treatment of AD. Data from studies on dupilumab showed no difference in responses among patients with immunoglobulin E or filaggrin mutations as well as robust down regulation of important inflammatory markers in biopsies of lesional skin. In addition, keratin 16, a marker for hyperplasia, showed a dose-response to dupilumab, said Dr Guttman. “This tell us dupilumab impacted inflammation and barrier dysfunction and established T_H2 axis as a truly pathogenetic in AD, as well as showed AD is a reversible and immune-drive disease like psoriasis,” she added.

Lebrikizumab and tralokinumab both target the IL-13 cytokine and have potential as therapeutic agents to treat AD. While study of tralokinumab has been flawed due to topical steroid use, a phase 2 study of lebrikizumab showed similar efficacy as dupilumab at 2-week and 4-week doses. These data suggests that IL-13 may be a primary cytokine in AD, she added.

IL-31 is known as the itch cytokine. The efficacy of nemolizumab, an IL-31 inhibitor, has been assessed in a phase 2b study and showed great efficacy for itch but modest improvement on disease severity, stated Dr Guttman.

Dr Guttman also highlighted a National Institute of Health-funded study (of which she is an investigator) that assessed the effect of ILV-094, an anti-IL-22 inhibitor that failed trials for rheumatoid arthritis and psoriasis, on AD. IL-22 promotes hyperplasia and impairs terminal differentiation. Dr Guttman reviewed data from the small placebo-controlled study that showed efficacy differentiation in dosage, significant improvements at week 8, and an association between efficacy and severity. In assessments of biopsies stratified by high baseline IL-22 expression vs low baseline IL-22 expression, biopsies of lesions with high IL-22 expression showed high response while those with low expression had no improvements and even exacerbation. “We think this is the first example of personalized medicine,” said Dr Guttman.

Other therapies in the pipeline include GBR-830 and KHK, which target 0x40, and abrocitinib, upadacitinib, and baricitinib, Januse kinase inhibitors.

Dr Guttman ended her presentation by discussing how the translational revolution in AD may also help patients with alopecia areata. Many patients with AD also have alopecia areatam and atopy is generally the highest comorbidity among patients with alopecia areata, Dr Guttman said. She showed clinical images from case reports that showed significant improvement among patients with alopecia areata treated with dupilumab.

“This is a very exciting time in inflammatory skin diseases,” Dr Guttman concluded.

For more coverage of IAS 2020, visit the newsroom.

—Melissa Weiss

Reference

Guttman E. New therapeutic advances in atopic dermatitis. Presented virtually at: Interdisciplinary Autoimmune Summit 2020; July 10-July 12, 2020.