Abstract: TH-PO295
Influence of Concomitant Opioid Medications on Antipruritic Effect and Safety of Difelikefalin in Patients on Hemodialysis
Session Information
- Hemodialysis and Frequent Dialysis - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 801 Dialysis: Hemodialysis and Frequent Dialysis
Authors
- Burton, James, University of Leicester Department of Cardiovascular Sciences, Leicester, United Kingdom
- Schaufler, Thilo, CSL Vifor, Glattbrugg, Switzerland
- Grewal, Satkiran, CleanSlate Centers Inc, Philadelphia, Pennsylvania, United States
- Ruessmann, Despina, CSL Vifor, Glattbrugg, Switzerland
- Lowe, Murray, CSL Vifor, Glattbrugg, Switzerland
- Wen, Warren, Cara Therapeutics Inc, Stamford, Connecticut, United States
- Fishbane, Steven, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, United States
Background
Pruritus is a known side-effect seen with mu-opioid receptor agonists, and hemodialysis (HD) patients receive such treatments. Difelikefalin (DFK) is a selective kappa-opioid receptor agonist indicated to treat moderate to severe CKD-associated pruritus (CKD-aP) in patients on HD. This exploratory post-hoc analysis assesses if using concomitant opioid medications affects efficacy or safety of DFK.
Methods
Phase-3 clinical studies KALM-1 & -2 randomized patients to receive either DFK or placebo (PBO) for 12 weeks after each HD session. Itch severity was measured daily with the Worst Itching Intensity Numerical Rating Scale (WI-NRS); patients indicated their worst itch intensity in the past 24 hours from 0 (no itch) to 10 (worst itch imaginable). We analyzed pooled KALM study data based on concomitant exposure to opioid medications.
Results
Of patients randomized to DFK/PBO, 24.2%/30.4% received other opioids. In both groups the likelihood of achieving improvements at 12 weeks in weekly mean WI-NRS scores of ≥3point, ≥4point or complete response (defined as ≥80% of daily scores 0 or 1) was not influenced by exposure to opioids (Figure).
Concomitant opioid medication use was associated with a higher incidence of treatment-emergent adverse events (TEAEs) in both the DFK and PBO groups. Patients receiving opioids experienced TEAEs at a rate of 44.7% (DFK) & 38.0% (PBO) compared to 19.0% (DFK) & 15.9% (PBO) in those not on opioids. The incidence of severe TEAEs was 22.3% (DFK) & 23.3% (PBO) in patients using opioids compared to those who were not (10.9% for DFK & 8.1% for PBO).
Conclusion
Concomitant use of opioid medications did not influence the efficacy of DFK to relieve CKD-aP in HD patients. The increase in TEAEs in patients prescribed concomitant opioids in either the DFK or PBO arms indicates the importance of carefully evaluating polypharmacy, especially continuation of opioid treatments in HD patients treated with DFK for CKD-aP.
Funding
- Commercial Support – Vifor Fresenius Medical Care Renal Pharma, Cara Therapeutics