Difelikefalin: A New κ-Opioid Receptor Agonist for the Treatment of Hemodialysis-Dependent Chronic Kidney Disease–Associated Pruritus

Abstract

Objective: To review data for difelikefalin (Korsuva) intravenous solution for management of moderate-to-severe pruritus in hemodialysis (HD) patients. Data Sources: Literature search of PubMed (January 1946-May 2022) and SCOPUS (January 1946-May 2022) was performed using the terms: Korsuva, CR845, and difelikefalin. Additional information sources include ClinicalTrials.gov, prescribing information, meeting posters, and references of identified articles. Study Selection and Data Extraction: Clinical trials and articles evaluating difelikefalin for chronic kidney disease–associated pruritis (CKD-aP) in HD patients. Data Synthesis: Difelikefalin is a peripherally acting κ-opioid receptor agonist with antipruritic effects for HD patients with moderate-to-severe CKD-aP. A phase 3 study showed significant improvement of patient itch intensity and itch-related quality of life (QOL) when compared with placebo. More patients had decreased pruritus on the 24-hour Worst Itch Intensity Numerical Rating Scale with difelikefalin (49.1%) compared with placebo (27.9%, P < 0.001). A positive effect was seen with or without use of additional antipruritic agents. Common adverse events include diarrhea, dizziness, and vomiting; there were no signs of physical dependence or centrally acting opioid effects (euphoria, hallucinations). Relevance to Patient Care and Clinical Practice: Difelikefalin reduced itch intensity and improved QOL for patients with CKD-aP. Whether the benefit is continued long-term as well as how it compares with other effective agents is currently unknown. Conclusion: Difelikefalin is the only Food and Drug Administration–approved treatment for moderate-to-severe CKD-aP with additional research into its benefit in this and other types of pruritus ongoing.

Comparative efficacy of Chinese herbal medicines for dialysis patients with uremic pruritus: A systematic review and network meta-analysis

“…Forth, minor improvement of VAS manifests limited role of CHM in relieving uremic pruritus in dialysis patients. Last, about thirty percent of UP patients benefits from placebo effect while comparing to Difelikefalin ( Fugal and Serpa, 2022 ). However, lack of placebo comparison in control groups from included RCTs in our study might affect the result of effectiveness.…”

“…The pathophysiology of UP is complicated; it is associated with various inflammatory mediators, neurotransmitters, and opioids. Treatments for UP, including difelikefalin, gabapentin, antihistamines, and phototherapy, have anti-pruritic effects, although adverse drug reactions (ADR), such as diarrhea, vomiting, somnolence, and dizziness, have been reported for some ( Hercz et al, 2020 ; Trachtenberg et al, 2020 ; Fugal and Serpa, 2022 ; Ko et al, 2022 ). The use of UVB radiation in phototherapy is associated with an increased risk of malignancy ( Mettang and Kremer, 2015 ).…”

Neurotrophin-4 and Brain-Derived Neurotrophic Factor Serum Levels in Renal Transplant Recipients with Chronic Pruritus

“…Studies proved that, by reducing pruritus intensity, difelikefalin improves the quality of life for patients with CKD-aP. However, the lack of data about its long-term effectiveness is a limitation that further research needs to overcome [ 43 ]. The search for alternative CKD-aP treatment is still ongoing.…”

Opioids and the Kidney: A Compendium

“… 66 , 67 Recently, the US Food and Drug Administration approved difelikefalin, a peripherally restricted and selective KOR agonist for moderate-to-severe CKD-aP. 68 Majority of trials show significant improvement of the CKD-aP conditions; however, no studies reported analyses of kidney function during the treatment. 69 , 70 Phase 3 clinical trials are currently underway for the safety and efficiency of difelikefalin in patients with CKD (Trial registration number NCT05342623 ).…”