I Hate Dialysis Message Board
Dialysis Discussion => Dialysis: News Articles => Topic started by: cassandra on December 15, 2019, 08:43:07 AM
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Novel Drug Eases Uremic Pruritus
Jody A. Charnow (https://www.renalandurologynews.com/author/jody-a-charnow-editor-50/)
In a phase 3 trial, difelikefalin, a kappa opioid receptor agonist, significant decreased itching and improved itching-related quality of life among dialysis patients suffering from pruritus.[/font]
WASHINGTON— Difelikefalin, an investigational kappa opioid receptor agonist that acts peripherally, is an effective treatment for pruritus in dialysis patients that leads to improvement in quality of life, according to the findings of the phase 3 KALM-1 trial presented at the American Society of Nephrology’s Kidney Week 2019 meeting.Difelikefalin is the first drug “that has demonstrated efficacy for this frustrating condition,” lead investigator Steven Fishbane, MD, a professor of medicine at the Feinstein Institutes for Medical Research at Northwell Health in Great Neck, New York, told attendees. No recognized standard of care exists for uremic pruritus.For the trial, Dr Fishbane and his collaborators randomly assigned 189 dialysis patients with pruritus to receive treatment with difelikefalin (0.5 mcg/kg) and 188 to receive placebo. The drug is administered intravenously at the end of a dialysis session, and its effects persist until the next dialysis treatment. Dr Fishbane explained that the difelikefalin cannot lead to abuse. “This drug is a small synthetic peptide. It is fully peripherally restricted so it doesn’t get into the CNS [central nervous system],” Dr Fishbane said. The drug has a high affinity for kappa opioid receptors and does not bind to the MU receptor to which the opioid drugs of abuse bind.From baseline to week 12, the proportion of patients achieving a 3-point or greater improvement in weekly mean score on the daily Worst Itch Numeric Rating Scale (WI-NRS) was significantly higher in the difelikefalin than placebo arm (51% vs 28%), Dr Fishbane reported. The difelikefalin group also had a greater proportion of patients who had a 4-point or greater improvement (39% vs 18%).Dr Fishbane also noted that the drug improved itch-related quality of life on 2 validated scales. From baseline to week 12, difelikefalin-treated patients experienced a 35% improvement over placebo using the 5-D Itch Scale and a 43% improvement over placebo using the Skindex-10 instrument.With regard to safety, the drug had a similar adverse event (AE) profile to placebo and was generally well tolerated. An AE of any type occurred in 68.8% of the difelikefalin group and 62.2% of the placebo group. AEs leading to treatment discontinuation occurred in 7.9% and 4.8% of patients, respectively. Serious AEs occurred in 25.9% and 21.8%, respectively.- Pruritus Common, Bothersome in Non-Dialysis CKD (https://www.renalandurologynews.com/home/news/nephrology/chronic-kidney-disease-ckd/pruritus-common-bothersome-in-non-dialysis-ckd/)Pruritus in Hemodialysis Patients Underestimated, Undertreated (https://www.renalandurologynews.com/home/news/nephrology/hemodialysis/pruritus-in-hemodialysis-patients-underestimated-undertreated/)For Treating Uremic Pruritus, Evidence is Strongest for Gabapentin (https://www.renalandurologynews.com/home/news/nephrology/hemodialysis/for-treating-uremic-pruritus-evidence-is-strongest-for-gabapentin/)Dr Fishbane pointed out that the difelikefalin group had a slight increase in the incidence of diarrhea and dizziness, both of which were mild and self-limited.Also at the conference, investigators presented findings of an analysis of 25,916 hemodialysis patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) showing that 37% of the patients reported being at least moderately bothered by pruritus, with the proportion ranging from 27% in Germany to 47% in the United Kingdom.The study, by Nidhi Sukul, MD, of the University of Michigan in Ann Arbor, and colleagues, also found that patients who were moderately bothered and extremely bothered by pruritus had significant 13% and 30% increased risks for death, respectively, in adjusted analyses compared with a reference group of patients not at all bothered by itching.ReferenceFishbane S, Jamal AZ, Wen W, et al. Efficacy and safety of difelikefalin in patients undergoing hemodialysis with pruritus: Results from a phase 3 randomized, controlled study (KALM-1). Presented at the American Society of Nephrology’s Kidney Week 2019 meeting held November 5-10 in Washington, DC. FR-OR134.Sukul N, Karaboyas A, Rayner HC, et al. Pruritus and mortality in hemodialysis patients: Results from the International DOPPS. Presented at the American Society of Nephrology’s Kidney Week 2019 meeting held November 5-10 in Washington, DC. Poster TH-PO243. https://www.asn-online.org/education/kidneyweek/2019/program-abstract.aspx?controlId=3225390 (https://www.asn-online.org/education/kidneyweek/2019/program-abstract.aspx?controlId=3225390)From the December 01, 2019 Issue of Renal and Urology News (https://www.renalandurologynews.com/print-issue/renal-urology-news-nov-dec-2019-issue/)
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Is it effective? I'm not sure about it.