Pruritus also known as itchy skin is an irritating sensation that makes you want to scratch. Itchy skin is often caused by dry skin and is common in older adults, as skin tends to become drier with age. Difelikefalin, a peripherally specific selective agonist of Kappa Opioid Receptors (KORs), has been approved for the treatment of pruritus is secondary to chronic kidney disease. KORs were first associated with itching in 1984 yet not much is known in non-US populations.

A new study in New England Journal of Medicine states that Intravenous administration of difelikefalin reduced itching and improved quality of life in patients with moderate to severe pruritus who were undergoing maintenance hemodialysis.
The study was double-blind, placebo-controlled, phase 3 trial in Japan, patients with moderate to severe pruritus were randomly allocated 1:1 to receive either placebo or 0.5 μg/kg of difelikefalin three times per week intravenously for 6 weeks. The primary end point was change from baseline in the Worst Itching Intensity Numerical Rating Scale (NRS; 0 to 10; higher scores indicate more severe itching) score at week 4.
The key findings of the study are
• A total of 230 patients were screened, of whom 178 were randomly assigned to receive placebo (n=89) or difelikefalin (n=89).
• The change from baseline in the weekly adjusted mean NRS score (95% confidence interval) at week 4 in the placebo and difelikefalin groups was −1.09 (−1.47 to −0.70) and −2.06 (−2.45 to −1.66), respectively.
• The difference between the groups was −0.97 (−1.52 to −0.42), demonstrating that difelikefalin was superior to placebo (P<0.001).
• Prespecified secondary quality-of-life end points showed consistent improvement associated with difelikefalin.
• The incidence of treatment-related adverse events in the placebo and difelikefalin groups was 3 of 89 patients (3%) and 13 of 89 patients (15%), respectively, of which the majority in the difelikefalin group were gastrointestinal (e.g., constipation and abdominal discomfort).
Researchers concluded that “Intravenous difelikefalin reduced itching and improved quality of life in patients with moderate to severe pruritus who were undergoing maintenance hemodialysis.”
Reference: Ichiei Narita, M.D., Ph.D. naritai@med.niigata-u.ac.jp et al; Difelikefalin for Hemodialysis Patients with Pruritus in Japan; NEJM Evid 2023;2(11); DOI: 10.1056/EVIDoa2300094