Abstract
BACKGROUND: Difelikefalin is well-tolerated and reduces itch among adults undergoing haemodialysis (HD), with chronic kidney disease-associated pruritus (CKD-aP). OBJECTIVE: This study aims to explore the influence of baseline itch severity on difelikefalin treatment outcomes. DESIGN: Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg. We report key endpoints from 3105 by baseline itch severity, determined using the Worst Itching Intensity Numerical Rating Scale (WI-NRS [moderate: WI-NRS < 7; severe: WI-NRS ≥ 7]). PARTICIPANTS: Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline). MEASUREMENTS: The primary endpoint of 3105 was safety; secondary endpoints included reduction in itch intensity (WI-NRS), and improvements in itch-related quality of life (QoL; 5-D itch scale) and sleep quality (Sleep Quality Numerical Rating Scale). FINDINGS: Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively. No treatment-related deaths occurred, and there were no safety concerns according to baseline itch severity. By week 12, both groups reported residual 'mild itch' according to mean (SD) WI-NRS scores (moderate: 2.9 [2.2]; severe: 3.1 [2.3]). Approximately one in four participants demonstrated 'complete response' in itch reduction (moderate: 27.1%; severe: 25.0%). Clinically relevant improvements in itch-related QoL and sleep quality occurred among both subgroups. CONCLUSIONS: Difelikefalin was well-tolerated and effective in reducing itch in participants with moderate and severe baseline itch, supporting its broad use in a range of individuals on HD with CKD-aP.