Interim Analysis: Dupilumab Reduces Itch, Pain in Ichthyosis and EB

Dupilumab reduced both itch and pain in congenital ichthyosis and epidermolysis bullosa (EB), with no new safety issues, in an interim analysis presented during the late-breakers sessions at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida.

Medical student Kennedy Gallagher presented “Dupilumab Reduces Itch in Epidermolysis Bullosa and Congenital Ichthyosis: Interim Analysis from a Single-Site, Investigator-Initiated Pilot Study.”

Gallagher noted that IL-4 receptors have been shown to enhance itch responses in patients, and that in several case reports, dupilumab—an IL-4 receptor antagonist—has been shown to reduce itch, especially in the EB population.

“For this study, we sought out to assess the effectiveness of dupilumab in reducing itch in patients with EB and congenital ichthyosis,” Gallagher said. “Given the dose connection between IL-4 receptor signaling and chronic itch, we hypothesized that dupilumab would reduce in these populations, leading to overall improved quality of life, among other secondary measures. Although we did consider nemolizumab and JAK inhibitors for this study, the favorable safety profile of dupilumab along with the approval down to 6 months of age for use in atopic dermatitis patients led us to trial this agent initially.”

The study involves patients 6 months and older with a diagnosis of a genetic skin disorder and baseline itch numerical rating scale (NRS) of at least four on average and at least five at worst. It includes three phases: an 8-week observational period, a 16-week treatment period, and a 20-month extension for patients who meet the primary endpoint of the study.

The primary endpoint is at least a two-point reduction in the worst itch score in at least 50% of patients.

“We are comparing the mean worst itch from Weeks 9 to 16, which we're considering our active treatment period, to Weeks -8 to 0, which is our control period,” Gallagher said. “Studies have suggested that clinically significant reduction in itch is in the range of two to four for adults and three to four for children. We also assessed the impact of dupilumab treatment on pain, quality of life, and other objective sleep measures.”

The study includes 22 subjects so far, with the intention of enrolling at least 10 more.

The interim results for mean reduction in average itch and worst itch were significant across the board for both EB and ichthyosis groups, Gallagher said.

“Over half of our patients demonstrated a clinically significant reduction in itch, with at least a three-point reduction in their worst itch score at Week 16, and about a quarter of our patients demonstrated at least a four-point reduction in their worst itch scores at Week 16, with some variation in earlier weeks,” she said. “When looking at itch reduction over time, we see the same phenomena that we saw in atopic dermatitis settings, and that is that the majority of itch reduction while on dupilumab treatment occurred within the first 8 weeks of the study. Lastly, there was a tremendous shift in itch reduction and itch severity, with most of our patients ending up at Week 16 in the mild-to-moderate categories of itch.”

Reductions of more than 50% in both scratch duration and number of scratch events during sleep were observed in all patients.

Adverse events related to dupilumab treatment were consistent with those found in atopic dermatitis studies, with only three instances of mild-to-moderate injection site reactions and one instance of mild conjunctivitis.

While only six of the 16 patients who have reached the third phase of the study have reached Week 52, Gallagher notes that “the level of itch reduction has been maintained and even improved throughout the extension period.”

Reduction in pain, she said, was greatest in the EB group but significant across both groups. Clinically significant change in quality of life was greatest in adults when compared to children and infants.

“We are very excited about these results and are continuing to recruit EB patients for the study,” Gallagher said.