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Abstract: SA-PO401

Correlation of Serum Phosphate With Pruritus Severity and Response to Difelikefalin

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States
  • Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium
  • Fishbane, Steven, Northwell Health, Great Neck, New York, New York, United States
  • Budden, Jeffrey J., Vifor Pharma Ltd, Glattbrugg, Zurich, Switzerland
  • Morin, Isabelle, Vifor Pharma Ltd, Glattbrugg, Zurich, Switzerland
  • Menzaghi, Frederique, Cara Therapeutics Inc, Stamford, Connecticut, United States
  • Wen, Warren, Cara Therapeutics Inc, Stamford, Connecticut, United States
  • Lerma, Edgar V., University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States
Background

Chronic kidney disease-associated pruritus (CKD-aP) is often reported by hemodialysis (HD) patients, thought to result from inadequate serum phosphate (sP) control, but recent studies refute this. Difelikefalin (DFK) is a selective kappa opioid receptor agonist approved in the United States and Europe for treatment of moderate-to-severe pruritus in adults undergoing HD. DFK significantly reduced itch in the Phase 3 KALM-1 and -2 trials. This analysis determined the correlation of sP to pruritus severity and response to DFK.

Methods

The KALM trials enrolled HD patients with moderate-to-severe CKD-aP (mean weekly worst itch numerical rating scale (WI-NRS) >4 [KALM-1] or ≥5 [KALM-2]). Patients were randomized 1:1 to intravenous DFK 0.5 µg/kg or placebo (PBO) 3 times/week (Wk) for 12 wks. Correlation between sP and WI-NRS at baseline and Wk 12 was assessed, as well as response to DFK in patients with and without hyperphosphatemia (sP ≤5.5 vs >5.5 mg/dL) at baseline.

Results

In pooled data (DFK and PBO), patients with baseline sP ≤5.5 mg/dL (N=438) had similar baseline characteristics to patients with sP >5.5 mg/dL (N=407). Baseline WI-NRS (7.1±1.4 vs 7.2±1.5) and anti-itch medication use (37.9% vs 38.1%) were similar. No correlation was observed between WI-NRS and sP values at baseline (p=0.54) [Figure] or Wk 12 (p=0.27). Clinically relevant improvement in WI-NRS following DFK treatment was similar in sP subgroups ≤5.5 vs >5.5 mg/dL (39.3% vs 40.2% for ≥4-point improvement; 51.1% vs 57.6% for ≥3-point improvement) and a significantly higher proportion of patients in the DFK group vs placebo reported a ≥4-point improvement in both sP subgroups (p≤0.017).

Conclusion

sP did not correlate with pruritus severity or response to DFK in patients with CKD-aP.

Funding

  • Commercial Support – Vifor Pharma