Oral difelikefalin effective in reducing atopic dermatitis- associated pruritus: Study
USA: In a recent study, the researchers observed a rapid, significant anti-pruritic effect of difelikefalin (DFK) in an atopic dermatitis (AD) mouse model and in subjects having mild-to-moderate AD. The results of the study support DFK's role as an anti-pruritic agent for itch-predominant AD patients.
The findings were presented at the AAAAI annual meeting 2022 and subsequently published in the Journal of Allergy and Clinical Immunology.
Many AD patients exhibit itch that is disproportionate to rash. In AD, only limited therapies specifically target itch. Difelikefalin is a selective kappa-opioid receptor agonist that is being developed for chronic pruritic conditions.
In the phase 2, randomized, double-blind study, Brian Kim, Washington University School of Medicine, and colleagues enrolled adults with AD and moderate-to-severe pruritus. They received oral placebo (PBO) or DFK (0.25, 0.5, or 1.0 mg) BID for 12 weeks. Also, mice with topical MC903-induced AD were treated with DFK (0.5 mg/kg) intraperitoneally and itch was assessed early (30 minutes).
Change from baseline in mean Itch Numerical Rating Scale (I-NRS) and >_4-point improvement in I-NRS at week 12 were the primary and key secondary endpoints.
The research led to the following findings:
- In mice, DFK promoted rapid, significant itch reduction independently of skin inflammation.
- Among 401 subjects randomized, ;64% had mild-to-moderate AD.
- In the overall population, treatment difference in mean I-NRS change between the combined DFK group (all doses) and PBO was 20.43 at week 12.
- In subjects with mild- to-moderate AD, a significant difference in mean I-NRS was observed at week 12 (20.75) in the DFK group versus PBO (P50.036); a significantly greater proportion of subjects achieved >_4-point improvement in I-NRS with DFK. Itch reduction was observed early (week 1).
- Adverse events with DFK were most commonly abdominal pain, nausea, dry mouth, head- ache, dizziness, and hypertension.
"We observed a rapid, significant anti-pruritic effect of DFK in an AD mouse model and in patietns with mild-to-moderate AD," wrote the authors. "The findings supports DFK's role as an anti-pruritic agent for patients with itch-predominant AD."
Reference:
The study titled, "Oral Difelikefalin Reduces Atopic Dermatitis–Associated Pruritus," was published in the Journal of Allergy and Clinical Immunology.
DOI: https://doi.org/10.1016/j.jaci.2021.12.075
KEYWORDS: atopic dermatitis, difelikefalin, pruritis, Journal of Allergy and Clinical Immunology, anti-pruritic, AAAAI annual meeting 2022, skin inflammation, skin disease, itching, rash
