Effectiveness of Nemolizumab in Improving Dialysis-Associated Pruritus Refractory to Difelikefalin: A Case Report.

Chronic kidney disease-associated pruritus (CKD-aP) is a common and distressing symptom among patients undergoing maintenance hemodialysis and is known to significantly impair quality of life. In contrast, prurigo nodularis (PN), characterized by intensely pruritic nodules, may develop as a result of persistent scratching due to chronic pruritus. While difelikefalin, a peripherally acting κ-opioid receptor (KOR) agonist, has been approved for the treatment of CKD-aP, alternative therapeutic options have not been sufficiently explored in patients who show an inadequate response. Herein, we report a case of a 74-year-old man on long-term dialysis who presented with severe CKD-aP (PP-NRS 9-10) and multiple pruriginous nodules. Although partial improvement was achieved with difelikefalin, moderate pruritus (PP-NRS 7) and residual nodules persisted. Nemolizumab, an interleukin-31 receptor α (IL-31Rα) antagonist approved for the treatment of PN, was subsequently introduced. After two doses, the patient experienced complete resolution of pruritus and marked flattening of nodular lesions. Elevated serum IL-31 levels have been reported in both PN and dialysis-related pruritus, suggesting a shared pathophysiological role of IL-31 in these conditions. The rapid and dramatic response to nemolizumab in this case supports the potential of IL-31 inhibition as a promising treatment strategy for patients with CKD-aP who are unresponsive to KOR agonists. This case represents the first report of sequential use of difelikefalin and nemolizumab for dialysis-associated pruritus and highlights the need for further studies to evaluate the efficacy of IL-31-targeted therapies in this setting.