Difelikefalin is a drug which is a selective agonist of kappa opioid receptors considered to be important in modulating pruritus in conditions such as chronic kidney disease.

Methods

• Double-blind placebo-controlled, phase 3 trial
• Patients undergoing haemodialysis who had moderate-to-severe pruritus were randomly assigned to receive either intravenous difelikefalin (at a dose of 0.5µg per kilogram of body weight) or placebo three times per week for 12 weeks
• Primary outcome was the percentage of patients with an improvement (reduction) of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale.
• Secondary outcomes included the change from baseline in itch-related quality of life measures, the percentage of patients with an improvement of at least 4 points in the WI-NRS score at week 12, and safety.

Results

• The imputed percentage of patients with a decrease of at least 3 points in the WI-NRS score was 49.15 in the difelikefalin group, as compared with 27.9% in the placebo group (P<0.001)
• The drug also resulted in a significant improvement from baseline to week 12 in itch-related quality of life

Conclusion

• Patients showed a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo.

Hence, it was established that treatment with difelikefalin for 12 weeks resulted in a marked and rapid reduction in itch intensity among patients undergoing haemodialysis who had chronic kidney disease-associated pruritus.

References

1. Fishbane S, Jamal A, Munera C, Wen W, Menzaghi F. A phase 3 trial of difelikefalin in haemodialysis patients with pruritus. New England Journal of Medicine. DOI: 10.1056/NEJMoa1912770