BACKGROUND: Pruritus is a common condition in chronic kidney disease (CKD), especially for patients receiving haemodialysis. CKD-associated pruritus (CKD-aP) can be distressing and have a negative impact on quality of life (QoL). This post hoc analysis aimed to assess the relationship between pruritus relief and QoL. METHODS: Data from phase 3 trials [(NCT03422653, NCT03636269 grouped), and NCT03998163] of the novel antipruritic difelikefalin (N = 914) were used to assess the relationship between reductions in pruritus intensity at Week 12 (24-h Worst Itching Intensity Numeric Rating Scale; WI-NRS), perceived improvement in itch (Patient Global Impression of Change, PGI-C) and pruritus-related QoL (Skindex-10 questionnaire). RESULTS: Patients receiving difelikefalin had greater improvements in Skindex-10 total scores than those receiving placebo [LS mean treatment difference -3.4; 95% confidence interval (CI) -5.5, -1.3; P = .002] and greater improvements across Skindex-10 domains (disease, mood and social functioning) at Week 12. In patients receiving difelikefalin, those with clinically meaningful improvements in pruritus (≥3-point reduction in WI-NRS score) at Week 12 had a greater improvement in Skindex-10 total score (mean difference 14.2; 95% CI 11.0, 17.3; P < .001) and Skindex-10 domains than those with a <3-point reduction in WI-NRS score. Improvements in Skindex-10 total scores correlated with PGI-C. CONCLUSIONS: Improvements in pruritus intensity following 12 weeks of treatment with difelikefalin were associated with improvements in QoL. Larger improvements in Skindex-10 scores were seen in patients with a greater reduction in pruritus intensity, indicating that improvements in pruritus are associated with a range of factors, such as mood and social functioning, that affect pruritus-related QoL.

BACKGROUND: Poor sleep quality is associated with higher mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis (HD). This post hoc analysis of the Phase 3 difelikefalin studies (Study 3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in individuals with CKD-aP improved sleep quality. METHODS: Itch intensity was assessed in patients undergoing HD who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1 and -2) or placebo (N = 425, KALM-1 and -2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D Itch Scale (5-D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS). RESULTS: Greater improvements in sleep quality were observed in patients with ≥3-point versus <3-point WI-NRS improvement using SQ-NRS in Study 3105 [mean (95% confidence interval) -5.2 (-5.6, -4.8) vs -1.5 (-2.0, -1.0)] and 5-D SDQ in KALM-1 and -2 [-1.8 (-2.1, -1.6) vs -0.8 (-1.1, -0.4)]. SQ-NRS and WI-NRS scores were highly correlated at both baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM-1 and -2. CONCLUSIONS: In patients undergoing HD with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief. TRIAL REGISTRATION: KALM-1 (NCT03422653), KALM-2 (NCT03636269), Study 3105 (NCT03998163).