Difelikefalin effective against pruritis in CKD patients

A new study published in Journal of the American Academy of Dermatology shows that oral difelikefalin effectively decreased moderate-to-severe pruritus in stage 3-5 chronic kidney disease (CKD) patients, recommending further research for this disease.

Patients with chronic renal disease must deal with the burden of persistent pruritus. Patients with NDD-CKD who experience pruritus can only use off-label medications as approved therapy.

Topical corticosteroids and antihistamines offer conflicting evidence, although gabapentinoids have been shown to be effective in clinical investigations with hemodialysis (HD) patients. Gil Yosipovitch and colleagues conducted this study to assess the effectiveness and safety of difelikefalin in decreasing itching in participants with non-dialysis-dependent CKD and those receiving hemodialysis.

Non-dialysis-dependent CKD (stages 3-5) and HD individuals with moderate-to-severe pruritus were included in this phase 2 randomized, double-blind, placebo-controlled dose-finding research. For 12 weeks, subjects were randomly assigned to either oral difelikefalin (0.25, 0.5, or 1.0 mg) or placebo. At week 12, the major end point was the change in the weekly mean Worst Itching Intensity Numeric Rating Scale (WI-NRS) score.

The key findings of this study were:

1. A total of 269 participants were randomly assigned (mean [SD] baseline WI-NRS: 7.1 [1.2]).

2. At week 12, difelikefalin 1.0 mg substantially reduced weekly mean WI-NRS scores compared to placebo (P =.018), with numerical reductions seen with difelikefalin 0.25 and 0.5 mg.

3. At week 12, 38.6% of participants on difelikefalin 1.0 mg had a full response (WI-NRS 0-1) compared to 14.4% on placebo. Difelikefalin improved itch-related quality-of-life indicators by 20%.

4. Dizziness, falls, constipation, diarrhoea, gastroesophageal reflux disease, tiredness, hyperkalemia, hypertension, and urinary tract infection were the most prevalent treatment-emergent side events.

Over a 12-week period, oral difelikefalin 1.0 mg effectively decreased itch in participants with moderate-to-severe pruritus related to stage 3-5 CKD. The findings of this phase 2 trial support the use of kappa opioid receptor activation to treat systemic itch associated with CKD prior to dialysis. These findings support additional investigation of this group, notably advanced CKD patients, as well as the advancement of oral difelikefalin in ongoing phase 3 studies.

Reference: 

Yosipovitch, G., Awad, A., Spencer, R. H., Munera, C., & Menzaghi, F. (2023). A phase 2 study of oral difelikefalin in subjects with chronic kidney disease and moderate-to-severe pruritus. In Journal of the American Academy of Dermatology. Elsevier BV. https://doi.org/10.1016/j.jaad.2023.03.051