New therapies for chronic pruritus of unknown origin (CPUO) could be close, Gil Yosipovitch, MD, said during his presentation, “What’s Best and What’s Next for Systemic Itch and CPUO” at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida.
“These are patients based on diagnosis of exclusion,” Dr. Yosipovitch said. “About 10% of patients with itch have this unspecified origin, and many of these patients are elderly—and do remember, a lot of times the elderly patients have itch. Most probably there is some immunosenescence and the Type 2 immune expression. There's also an imbalance in these patients between mu and kappa opioids.”
Dr. Yosipovitch acknowledged that biologics and JAK inhibitors make sense as potential treatments for CPUO, and he noted that dupilumab is currently being studied for it.
“It wouldn't surprise me that both other IL-13s, whether it would be tralokinumab or lebrikizumab, would be helpful,” he said. “Also, in a case series, JAK stat inhibitors worked extremely well for these miserable patients.”
Dr. Yosipovitch also noted that nemolizumab’s targeting of IL-31 makes it a promising option.
“It has been approved for [purigo nodularis] and [atopic dermatitis], so most thought it would work quite well. I'm quite sure there have been already some case reports or at least colleagues of mine who are submitting these case reports. But it works extremely well for chronic pruritus of undetermined origin. So, hopefully, this will also be tested.”
Additionally, Dr. Yosipovitch discussed MRGPRX2 inhibitors, which have demonstrated positive results in animal testing.
“This receptor has, until recently, exclusively been reported only in mast cells,” he said. “But there are some new data to suggest that it's also on the nerve fiber, but it's a very explosive receptor for treatment of itch. And I encourage the industry to target this G coupled protein cell receptor because the potential here is very big.”