Meaningful Improvement Thresholds for Pruritus and Sleep Disturbance in PBC Using the Worst Itch and Sleep Interference Numerical Rating Scales.

INTRODUCTION: Cholestatic pruritus is common in primary biliary cholangitis (PBC), adversely affecting quality of life. This study aimed to establish the within-patient meaningful change threshold (MCT) for the Worst Itch Numerical Rating Scale (WI-NRS) in patients with PBC and pruritus. Determining MCTs for patient-reported outcomes is crucial for interpreting treatment efficacy in clinical trials. Given the high impact of pruritus on sleep in PBC, an MCT was also estimated for the Sleep Interference NRS (SI-NRS), which assesses pruritus-related sleep interference. METHODS: Analyses were performed on blinded data from the Phase 3 GLISTEN study of linerixibat in patients with PBC and moderate-to-severe pruritus (NCT04950127). Anchor-based methods included the Patient Global Impression of Severity (PGI-S) and Change (PGI-C) as primary and supportive anchors, respectively. Correlations between weekly averages of daily WI-NRS and SI-NRS change scores and the anchors were assessed. A '1-point' improvement in PGI-S and 'moderately improved' on PGI-C were considered key reference groups for MCT determination. MCTs were evaluated in patients who reported changes in their itch and/or sleep were meaningful, as indicated by PGI-C item 2. Cumulative distribution function curves and distribution-based methods provided supporting evidence. RESULTS: Data from 238 patients were included. Among patients reporting meaningful change in itch at Week 24, mean (standard deviation) change in WI-NRS was - 3.0 (1.7) for the '1-point' PGI-S improvers and - 2.9 (2.0) for the 'moderately improved' PGI-C group. Corresponding values for SI-NRS were - 2.6 (2.1) and - 2.4 (2.1). Distribution-based estimates for the change in WI-NRS and SI-NRS each ranged from 0.42 to 0.85. CONCLUSION: This study demonstrated that a reduction of ≥ 3 points in WI-NRS and ≥ 2.5 points in SI-NRS weekly scores represent clinically meaningful improvement thresholds for patients with PBC and moderate-to-severe pruritus. These results support use of WI-NRS and SI-NRS in future PBC trials evaluating new treatments for pruritus.