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Abstract Background Difelikefalin, a potent and highly selective agonist of kappa opioid receptors, is used to treat moderate-to-severe pruritus in hemodialysis patients. Methods This was a 52-week, open-label phase 3 trial following a 6-week randomized double-blind placebo-controlled treatment period to investigate the efficacy and safety of difelikefalin in Japanese hemodialysis patients. Having completed the 6-week double-blind period, patients received difelikefalin 0.5 μg/kg three times per week intravenously for 52 weeks. Efficacies were assessed using numerical rating scale (NRS) scores, proportion of patients whose NRS score improved by ≥ 3 points and ≥ 4 points, Shiratori severity score, proportion of patients with a nighttime Shiratori severity score of ≤ 2, the Skindex-16 score, 5-D itch scale score, and patient global impression of change (PGIC). Safety was assessed on the basis of adverse events, clinical laboratory tests, vital signs, body weight, 12-lead electrocardiography, and dependency. Results The number of patients who entered the extension treatment period from the difelikefalin (MR–MR) and placebo (P-MR) groups was 85 and 83, respectively. The weekly mean NRS scores (mean ± SD) in the MR–MR group at baseline, week 6, and week 58 were 6.57 ± 1.32, 4.04 ± 2.24, and 2.36 ± 1.86, respectively. The weekly mean scores in the P-MR group, at baseline, week 6, and week 58 were 6.42 ± 1.29, 4.85 ± 1.90, and 2.73 ± 2.14, respectively. In patients receiving difelikefalin, there was a decline in the score from treatment initiation, and this decline continued until week 58. Similarly, improvements were seen until week 58 in the proportion of responders, Shiratori severity score, proportion of responders based on the Shiratori severity score, the Skindex-16 score, 5-D itch scale score, and PGIC. A correlation was seen between the change in NRS and itch-related quality of life (QOL), including the Shiratori severity score, Skindex-16 score, 5-D itch scale score, and PGIC. Difelikefalin was well tolerated and safe even when used long term. Conclusions Difelikefalin improved itching and itch-related quality of life during long-term treatment in hemodialysis patients with moderate-to-severe pruritus whose response to conventional medications had been inadequate. It also demonstrated excellent safety and tolerability. Trial registration: ClinicalTrials.gov; NCT04711603. Registered 15 January 2021, https://www.clinicaltrials.gov/study/NCT04711603?term=NCT04711603&rank=1 .

Abstract Background Hemodialysis-associated pruritus (HAP) occurs in 60–80% of hemodialysis patients. This significant complication not only decreases quality of life through sleep disturbance and depression, but also leads to poor survival outcomes. The polymethylmethacrylate (PMMA) membrane was the first synthetic polymer membrane for the hollow-fiber artificial kidney created in 1977. PMMA membrane dialyzers have been reported to be effective for improving various complaints, including pruritus, and nutritional status. In Japan, a PMMA membrane hemodiafilter Filtryzer® PMF™-A (PMF-A) was launched in November 2021 and subsequently became available for online hemodiafiltration (OHDF). This study aimed to determine whether PMF-A effectively improves pruritus in hemodialysis patients. Methods Participants were 20 patients (median age 74.5 years) on predilution OHDF (pre-OHDF) or postdilution OHDF (post-OHDF) using an Asymmetric Triacetate Membrane® hemodiafilter (FIX-210E eco or FIX-210S eco), who were experiencing pruritus of “very mild” or higher severity based on the Shiratori severity score either during the daytime or nighttime. After switching to post-OHDF with PMF-21A (substitution flow rate: 10 L/session), the substitution flow rate was gradually increased according to results of pruritus evaluation every 2 weeks over 3 months. The primary endpoint was the severity of pruritus evaluated using visual analogue scale (VAS) and the Shiratori severity score. Secondary endpoints included white blood cell count (WBC), hemoglobin level (Hb), platelet count (Plt), serum albumin level (Alb), high-sensitivity C-reactive protein (hsCRP), IL-6, dry weight (DW), and solute removal performance. Results The median VAS score was significantly decreased 2 weeks after switching compared with baseline (44 mm) and remained significantly decreased at Week 12 (22 mm; p

Abstract Background Hemodialysis-associated pruritus (HAP) is a serious complication that occurs in 60–80% of hemodialysis patients, which not only decreases quality of life but also worsens prognosis. We have developed a treatment algorithm to take a comprehensive cause-specific approach to HAP and used it at our facility since June 2009. In this treatment algorithm, moisturizers and topical steroids are used depending on skin condition and severity of pruritus; administration of nalfurafine hydrochloride is considered in treatment-resistant cases. If pruritus improves, we attempt to taper topical steroids by switching to lower potency or by dose reduction or discontinuation. Here, we examined the effectiveness of the treatment algorithm over 9 years in terms of changes in medications. Methods Subjects were hemodialysis patients who received treatment for HAP at our facility: 89 in May 2009 before introduction of the algorithm, and 131 in April 2013, 164 in October 2014, 190 in October 2015, 181 in October 2016, 215 in October 2017, and 224 patients in October 2018 after its introduction. A questionnaire survey was conducted on the presence of pruritus, severity (using a visual analogue scale [VAS] and Shiratori severity scores), frequency, and insomnia due to pruritus. Changes in medications were investigated using medical records and compared. Results The proportion of patients with pruritus decreased significantly from 96.6% in 2009 to 66.8% in 2018 (p < 0.001). Median VAS score significantly decreased from 53.0 mm in 2009 to 24.5 mm in 2018 (p < 0.001), and the proportion of patients with insomnia due to pruritus also significantly decreased from 25.8% in 2009 to 2.2% in 2018 (p < 0.001). The proportion of patients who used moisturizers significantly increased from 34.8 to 89.7% (p < 0.001). The proportion of patients receiving topical steroids decreased from 47.2 to 35.7%, but the difference was not significant (p = 0.085). Conclusions The treatment algorithm was shown to be useful for improving HAP, but future challenges were identified, including promoting use of lower potency topical steroids or discontinuation. Further prospective studies are required to confirm the role of each treatment intervention in a comprehensive cause-specific approach to HAP.

Abstract Background Pruritus in patients undergoing hemodialysis reduces quality of life via insomnia and depression, and negatively affects prognosis. For diagnosing pruritus, selecting therapeutic strategies, and determining therapeutic outcomes, methods are needed for objectively quantifying the degree of itchiness. In 2015, the Japanese version of the 5-D itch scale (5D-J), originally developed in the USA in 2010, was developed as a simple self-administered questionnaire; it evaluated the degree of itchiness based on five components: (1) duration of itchiness, (2) degree of itchiness, (3) direction of itchiness, (4) disability caused by itchiness, and (5) distribution of itchiness. 5D-J is useful for comprehensively assessing multiple elements related to itchiness. We used 5D-J to assess the degree of itchiness experienced by patients undergoing hemodialysis to investigate its clinical usefulness. Methods Subjects were 336 patients undergoing maintenance hemodialysis at our facility in October 2016; they were selected from 383 patients, of whom 20 were excluded because their itchiness had a dermatologic origin and 27 were excluded because their localized itchiness was related to vascular access, respectively. The status of itchiness (duration, degree, direction, disability, and distribution) of the patients was surveyed in October 2016 using 5D-J; total scores were calculated and used for assessing the itchiness experienced by patients. We additionally investigated whether 5D-J scores correlated with visual analog scale (VAS) and Shiratori severity scores for pruritus. Results Degree was reported as “not present” by 124 patients (36.9%), “mild” by 164 (48.8%), “moderate” by 46 (13.7%), “severe” by 2 (0.6%), and “unbearable” by 0 (0%). Total score was 5 points in 55 patients (16.4%), 6–9 in 176 (52.4%), 10–14 in 95 (28.3%), 15–19 in 9 (2.7%), 20–24 in 1 (0.3%), and 25 in 0 (0%). The 5D-J total and VAS scores were strongly correlated (r = 0.7159; p

Abstract: Pruritus is a condition in which itch occurs in the absence of apparent skin lesions. It is sometimes unresponsive to treatment with topical moisturizers and often is unresponsive to antihistamines. We evaluated the antipruritic effects of Neurotropin injections in patients with moisturizer‐ and antihistamine‐resistant pruritus. We monitored these patients by itch scores recorded in symptom diaries, as well as reports of quality of life (QOL). This study investigated both the efficacy and safety of Neurotropin injections using an open‐label study design. We enrolled 40 patients from six participating study sites. Of the 40 patients that were initially enrolled, six patients were ineligible, and ultimately, 33 were included for evaluation after one patient dropped out. Neurotropin was administered by subcutaneous injection to 22 patients and intravenous injection to 11 patients at a frequency of once per week. Compared to data collected during a one‐week observation period prior to treatment, after seven injections of Neurotropin, there was a significant improvement in the Shiratori symptom severity score and the visual analog scale (VAS) scores for itch symptoms, and the Dermatology Life Quality Index (DLQI) for quality of life. No new adverse events occurred during the period of investigation. A notable benefit to Neurotropin is that it can be used in patients with renal impairment and patients receiving dialysis therapy. Our results demonstrated that Neurotropin is effective in the treatment of moisturizer‐ and antihistamine‐resistant pruritus. [ABSTRACT FROM AUTHOR]