A novel interleukin (IL) antagonist currently in phase 2 studies could advance the treatment of atopic dermatitis (AD), according to Hensin Tsao, M.D., Ph.D., who spoke recently during the MauiDerm 2017 meeting.
The recently discovered IL-31 resides between Th2 cells and sensory neurons in the itch pathway, he says.
“It has a neural link, beyond an inflammatory link, as opposed to IL-4 and IL-13, which are much more immune related interleukins” impacted by dupilumab (Dupixent, Sanofi and Regeneron Pharmaceuticals), which earned U.S. Food and Drug Administration approval for AD earlier this year.
Dr. Tsao is professor of dermatology at Harvard Medical School and director of the Melanoma and Pigmented Lesion Center/Department of Dermatology at Massachusetts General Hospital.
In a phase 2 trial, blocking the IL-31 receptor A (IL-31RA) significantly improved itch in patients with AD.1 Even the lowest dose of the IL-31RA inhibitor nemolizumab (CIM331, Galderma) studied (0.1 mg, three doses one month apart) met researchers’ primary endpoint, achieving a 43.7% reduction in investigator assigned pruritus scores, versus 20.9% for placebo (p = 0.002), at week 12 .
Regardless of dose, Dr. Tsao says, “Most effects were notable by about three weeks.”
The drug also allowed patients to achieve Eczema Area and Severity Index (EASI) reductions of 23% to 40.9%. The most predominant adverse events (AEs) were AD exacerbation and peripheral edema, although investigators note that the trial’s limited size and duration preclude solid conclusions regarding AEs.
Dr. Tsao says, “This is a first-in-class humanized antibody against IL-31RA. It sits at the nexus between inflammation and itch sensation and provides important validation that there is a neurocutaneous element to many of the sensations” felt by people with eczema. “It may be more effective on the pruritus component. It’s not clear that, as a single agent, it will completely work on the inflammatory component. In fact, AD is exacerbated in some patients. It also may be useful in other forms of chronic itch.”
Additional research provides clues regarding how IL-31 could contribute to the sensation of itch, he says.
“Patients with familial primary localized cutaneous amyloidosis have a mutation in the oncostatin M receptor, which happens to bind with IL-31.2 Mutations in this oncostatin M receptor lead to hereditary pruritus, followed by amyloidosis. The receptor itself is part of the IL-31 receptor complex. We know that IL-31 is increased in itchy skin.”
Therefore, he says, it makes sense that blocking the signaling of this interleukin and receptor could potentially reduce itch.
Disclosures: Dr. Tsao is a consultant and medical advisory board member for Epiphany Dermatology. He is also on the scientific advisory board for Lubax and has received funding from the National Institutes of Health, the Melanoma Research Alliance and the U.S. Department of Defense, and serves as an editorial advisor for several dermatologic journals.
1. Ruzicka T, Hanifin JM, Furue M, et al. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826-835.
2. Arita K, South AP, Hans-Filho G, et al. Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis. Am J Hum Genet. 2008;82:73-80.