“Both basic science and clinical research have led to a more complete understanding of the multiple pathophysiologic factors that may be operative inherently in atopic skin and which contribute to clinical presentations of atopic dermatitis.”
That was a major message delivered today, Thursday, Oct. 1, by James Del Rosso, D.O., in his seminar, “New Approaches in Atopic Dermatitis,” on opening day of the Fall Clinical Dermatology Conference in Las Vegas.
“Regardless of whether the primary pathophysiologic events start ‘inside out’ or ‘outside in, many aberrations occur within the normal physiologic functions of skin that lead to clinical signs and symptoms,” Dr. Del Rosso says. “There is not a simple pathophysiologic switch that when you turn that switch off, the disease is cured. There are many switches involved, including barrier mechanisms, specific enzyme functions, various interleukins and cytokine pathways, and crosstalk pathways. All of these switches may help us find more effective therapeutic agents.”
READ: Managing severe atopic dermatitis
Beyond the current approaches—which include barrier repair, topical corticosteroid therapy and topical calcineurin inhibitor therapy—recent phase 3 data has become available on a boron-based topical phosphodiesterase E-4 (PDE4) inhibitor, crisaborole 2% ointment. Dr. Del Rosso notes that in the two phase 3 studies, subjects two years of age and older with mild or moderate atopic dermatitis applied either crisaborole ointment or vehicle ointment BID.
About one of three actively treated subjects were clear or almost clear, with at least a two-grade improvement in severity rating, which was statistically superior to the vehicle groups in both studies. At endpoint, about half the crisabolole-treated subjects were clear—which was 10 to 20% better than the vehicle-treated subjects. No serious adverse events and a very low discontinuation rate (1.2%) were reported.
“The phase 3 study data on crisaborole is very promising, especially since the results support that it is an effective and safe topical non-steroidal option that was also shown to reduce pruritus effectively and quickly,” Dr. Del Rosso says.
Another promising drug under development, this one for more severe cases of atopic dermatitis, is dipilumab, an injectable monoclonal antibody that targets IL-4 and IL-13. Dr. Del Rosso says four trials have yielded promising results.
“If dipilumab proves to be effective and safe in patients with severe atopic dermatitis, this will be a major breakthrough in dermatologic therapy,” he says.
Other oral agents for atopic dermatitis that have received recent attention are apremilast, an oral PDE4 inhibitor, and tofacitinib, a Janus kinase inhibitor.
In the interests of disclosure, Dr. Del Rosso has served as a consultant and speaker for Anacor; a consultant, speaker, and researcher for Celgene, an advisory board member for Pfizer, and a researcher for Regeneron. In addition to his Las Vegas practice, Dr. Del Rosso is adjunct clinical professor of dermatology) at Touro University College of Osteopathic Medicine in Henderson, Nev.