Targeted treatments for atopic dermatitis
Novel immunomodulators expected to usher in new therapeutic era
Emerging treatments are expected to help fill the need for safer and more effective therapies for atopic dermatitis (AD), says Emma Guttman-Yassky, M.D., Ph.D.
Speaking at the 2nd Inflammatory Skin Disease Summit, she discussed investigational topical and systemic medications for AD that are targeting the immune-mediated pathogenic pathways via novel mechanisms of action.
“Just 10 years ago, research aimed at developing new therapies for AD focused only on correcting the skin barrier abnormalities that are present with the disease. Based on increasing knowledge that AD is an immune-driven disorder and understanding of the inflammatory axes involved in the disease, new disease-specific immunomodulatory therapies have been developed that are showing promise for reversing both the skin barrier and immune abnormalities and with a favorable safety profile that may allow for long-term use,” says Dr. Guttman-Yassky, professor of dermatology and clinical immunology, Icahn School of Medicine at Mount Sinai, New York City.
“At the same time, we are seeing translation of advances in understanding of other inflammatory skin diseases into therapeutic developments,” she continues. “Ultimately, bringing better care for patients with these disorders will require bridging academic research with pharma, and the Inflammatory Skin Disease Summit was successful in contributing to that goal.”
Systemic treatment advances
Recognition that AD is a systemic disease and that up to one-third of affected individuals suffer with moderate-to-severe disease underscores the need for systemic treatments.
“Treatment targeting just the lesional skin with topical therapies can be ineffective for maintaining disease control in severe patients because AD is a systemic disease with abnormalities also present in the non-lesional skin that can perpetuate the condition.
Treatment with systemic medications is therefore needed to truly reverse the abnormalities in both lesional and nonlesional skin,” Dr. Guttman-Yassky explains.
Of the systemic treatments in development for AD, dupilumab (Dupixent, Regeneron/Sanofi) is the closest to becoming commercially available. Dupilumab is a monoclonal antibody that targets the TH2-centered inflammatory axis in patients with AD, binding to the shared alpha chain subunit of interleukin-4 (IL-4) and IL-13 receptors to inhibit IL-4 and IL-13 signaling. Analyses of skin biopsy specimens from patients with AD who were treated with dupilumab show that it suppresses inflammation and also reverses the epidermal hyperplasia and differentiation abnormalities that are present with AD.
“The coupling of the clinical and histological improvement with dupilumab is very important because it provides proof that the immune abnormalities perpetuate AD. In addition, it provides hope that dupilumab may be a safer alternative for systemic treatment because it does not suppress the entire immune system,” Dr. Guttman-Yassky says.
Other systemic treatments in development for AD include agents that target janus kinase (JAK), phosphodiesterase 4 (PDE 4), IL-22, IL-23, and IL-17.
“The fact that several pathways are implicated in the pathogenesis of AD raises the possibility that we may use different targeted therapeutic approaches for disease control,” says Dr. Guttman-Yassky.
“That is an exciting prospect, but we still need to learn which axis or axes will be the best target to successfully control AD and maintain disease remission long-term, and whether there are opportunities for a personalized medicine approach to treatment of AD. While it is still very early and there are many questions to be answered, we are very hopeful that we will be able to provide better care for our patients with AD.”