# Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate‐to‐Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis

## TL;DR

This study shows that difelikefalin reduces itch severity in hemodialysis patients with moderate or severe chronic kidney disease-related pruritus.

## Contribution

The study explores how baseline itch severity affects treatment outcomes with difelikefalin in hemodialysis patients.

## Key findings

- Difelikefalin reduced itch intensity to mild levels in both moderate and severe baseline groups by week 12.
- Approximately 25% of participants in both groups showed complete response to itch reduction.
- Improvements in quality of life and sleep quality were observed in both subgroups.

## Abstract

Difelikefalin is well‐tolerated and reduces itch among adults undergoing haemodialysis (HD), with chronic kidney disease‐associated pruritus (CKD‐aP).

This study aims to explore the influence of baseline itch severity on difelikefalin treatment outcomes.

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]).

Adult participants undergoing maintenance HD (n = 222) with mild‐to‐moderate CKD‐aP (WI‐NRS score ≥ 5 at baseline).

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).

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.

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.