Abstract: TH-PO294
Efficacy and Safety of Difelikefalin Compared with Placebo in Patients Receiving Concomitant Opioid Medication
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
Difelikefalin (DFK) is a selective kappa opioid receptor agonist approved to treat moderate to severe CKD-associated pruritus (CKD-aP) in patients on hemodialysis (HD). Pruritus is a known side effect of mu opioid receptor agonistic drugs, but it is unknown if their concomitant use influences the antipruritic effects or safety of DFK.
Methods
Phase-3 studies KALM-1 and -2 established the efficacy and safety of DFK over placebo (PBO) in HD patients with CKD-aP. Itch intensity was assessed with the weekly mean of the Worst Itching Intensity Numerical Rating Scale (WI-NRS) measured at baseline and after 12 weeks of treatment. Patients were asked daily for the worst itch intensity in the past 24 hours from 0 (no itch) to 10 (worst itch imaginable).
This exploratory post-hoc analysis of pooled KALM trial data assesses the efficacy and safety of DFK compared to PBO, dependent upon exposure to concomitant opioid medication.
Results
Of participants randomized to receiving DFK/PBO, 24.2%/30.4% were taking concomitant opioid medications. More patients treated with DFK vs. PBO achieved WI-NRS improvements of ≥3point, ≥4point and complete response (defined as ≥80% of daily scores 0 or 1) at week 12, regardless of their concomitant use of opioids (Figure).
More patients on concomitant opioids reported any non-fatal treatment emergent adverse event (TEAE) independent of treatment exposure (concomitant vs. no concomitant opioid exposure: DFK: 44.7% vs. 19.0%; PBO: 38.0% vs. 15.9%). Similarly, severe TEAEs were more common in patients on concomitant opioids (concomitant vs. no concomitant opioid exposure: DFK: 22.3% vs. 10.9%; PBO: 23.3% vs. 8.1%).
Conclusion
This exploratory analysis confirms that DFK can effectively relieve CKD-aP in HD patients despite the use of concomitant opioid medications. The higher rate of TEAEs in patients receiving either DFK or PBO in combination with opioids makes careful assessment of continued use of opioid medications advisable.
Funding
- Commercial Support – Vifor Fresenius Medical Care Renal Pharma, Cara Therapeutics