Effectiveness of difelikefalin in a new treatment algorithm for hemodialysis-associated pruritus: a prospective interventional study

Abstract Background Since June 2009, our facility has been using an internally developed treatment algorithm that facilitates a comprehensive approach to address each cause of hemodialysis-associated pruritus (HAP), wherein oral nalfurafine, a selective κ-opioid receptor (KOR) agonist, is used for patients resistant to conventional treatments. Upon approval of intravenous difelikefalin, a new KOR agonist, in Japan in December 2023, we revised the treatment algorithm. Here, we evaluated the effectiveness of difelikefalin in the new treatment algorithm. Methods Nalfurafine was administered for 6 weeks or longer to 43 patients who were receiving maintenance hemodialysis at our facility in order to treat treatment-resistant HAP in accordance with the treatment algorithm. In 9 of the 43 patients, response to nalfurafine was considered poor based on the presence of moderate or severe daytime or nighttime pruritus according to the Shiratori severity score, or the numerical rating scale (NRS) ≥4, despite good adherence confirmed through history taking. For those 9 patients, the medicine was switched to difelikefalin in April 2024 and administered for 16 weeks. The primary endpoint was pruritus severity according to the Shiratori severity score and the NRS. The secondary endpoints were the frequency of itching, presence/absence of pruritus-related insomnia, satisfaction with treatment, and presence/absence of adverse events. Results The numbers of patients with moderate or severe pruritus according to the Shiratori severity score were 4 (44.0%) during the daytime and 6 (66.7%) at nighttime before the change to difelikefalin. However, at week 16 after the change, both had decreased to 0 (0.0%) (p < 0.01, p < 0.001, respectively). The median [interquartile range] of the NRS was 5 [4, 7] before the change, which significantly decreased to 3 [2, 3] at week 16 after the change (p < 0.005). The number of patients with insomnia due to pruritus was 4 (44.4%) before the change, which significantly decreased to 0 (0.0%) at week 16 after the change (p < 0.01). No adverse events were observed. Conclusions In the new HAP treatment algorithm, difelikefalin was suggested to be a useful and safe medicine for patients on hemodialysis who are resistant to conventional HAP treatment.