Efficacy and Safety of Switching from Nalfurafine to Difelikefalin in Hemodialysis Patients with Refractory Pruritus

Background: Hemodialysis-associated pruritus is common and can substantially impair quality of life. Given its heterogeneous pathophysiology and variable treatment response, individualized therapeutic strategies are needed. This study investigated the prevalence and severity of pruritus and clinical outcomes after switching from nalfurafine to difelikefalin. Methods: Clinical data from 108 maintenance hemodialysis patients whose pruritus severity was assessed using the Numerical Rating Scale (NRS) were retrospectively reviewed. Ten patients with persistent moderate-to-severe pruritus (NRS ≥ 3) despite treatment with nalfurafine were switched to difelikefalin in routine clinical practice, of whom eight completed the 16-week follow-up and were included in the switch group. Eight patients matched for age, sex, dialysis vintage, and baseline NRS served as controls. Changes in NRS scores at weeks 4 and 16, as well as adverse events, were evaluated. Results: Among 108 patients, 21 (20%) had no pruritus, while 20 (18.5%), 47 (43.5%), and 20 (18.5%) had mild, moderate, and severe pruritus, respectively. Of 14 patients receiving nalfurafine, 13 (92.9%) had persistent moderate-to-severe pruritus. In the switch group, mean NRS decreased from 5.9 ± 1.7 at baseline to 2.3 ± 2.3 at week 4 and 2.0 ± 0.9 at week 16 (p = 0.0156 and p = 0.0078, respectively), with no meaningful change in controls. No serious adverse events strongly related to difelikefalin were identified. Conclusions: Pruritus was highly prevalent in this cohort. Switching to difelikefalin was associated with rapid and sustained improvement in patients inadequately responsive to nalfurafine, with favorable tolerability, supporting its potential role as an individualized treatment option.