Serum Phosphate, Difelikefalin, and Pruritus Severity in CKD

Steven N. Fishbane, MD, and colleagues conducted a post-hoc analysis of data from three phase III studies (KALM-1, KALM-2, and open-label Study 3105) involving difelikefalin, a novel antipruritic agent approved for the treatment of moderate to severe chronic kidney disease-associated pruritus (CKD-aP) in adults receiving hemodialysis.  

CKD-aP is associated with elevated serum phosphate (sP). This analysis examined the role of sP in the pathogenesis of CKD-aP as well as whether difelikefalin relieves CKD-aP in patients with and without elevated sP.  

The analysis included patients with moderate to severe CKD-aP undergoing hemodialysis with baseline sP data. Eight hundred forty-five participants were sourced from the KALM-1 and KALM-2 studies, and 220 participants were from Study 3105.  

The researchers assessed the correlation between 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score and sP. Among participants from KALM-1 and KALM-2, baseline characteristics in the overall population were similar in patients with sP ≤5.5 and >5.5 mg/dL. There was no significant correlation between WI-NRS and sP at baseline or in week 12. Similarly, no correlation was found between WI-NRS and sP at baseline or between their change from baseline to week 12 among patients receiving placebo (all P<.05).   

More participants receiving placebo with baseline sP ≤5.5 mg/dL experienced clinically meaningful (≥3-point) reductions in WI-NRS scores from baseline to week 12 than those receiving placebo with baseline sP >5.5 mg/dL (least squares mean 37.2% vs 27.4%; odds ratio, 0.63; 95% CI, 0.41-0.97; P=.04).  

A greater percentage of patients receiving difelikefalin achieved a ≥3-point WI-NRS reduction from baseline to week 12 compared with those receiving placebo. This was similar between sP ≤5.5 and >5.5 mg/dL subgroups (least squares means 51.1% vs 57.6%; P=.20). No significant relationships between sP and WI-NRS were observed in patients receiving difelikefalin in Study 3105 at any time point.  

In conclusion, there was no observed correlation between the severity of pruritus and sP or the response to placebo or difelikefalin among patients with CKD-aP receiving hemodialysis. Regardless of baseline sP, difelikefalin relieved itch when compared with placebo. 

Source: Kidney360