Establishing the Relationship Between the Worst Itch Numerical Rating Scale and EQ-5D Utility in Patients With Primary Biliary Cholangitis Experiencing Pruritus: Pooled Results From GLIMMER and the PRO Validation Study
Author(s)
Irina Proskorovsky, MSc1, Balazs Dobi, PhD2, Anna Halliday, MSc3, Zsofia Kiss, MSc4.
1PPD Evidera, Bethesda, MD, USA, 2PPD Evidera, Budapest, Hungary, 3GSK, London, United Kingdom, 4GSK, Munich, Germany.
1PPD Evidera, Bethesda, MD, USA, 2PPD Evidera, Budapest, Hungary, 3GSK, London, United Kingdom, 4GSK, Munich, Germany.
OBJECTIVES: Cholestatic pruritus is a common condition in primary biliary cholangitis (PBC) that can lead to poor health-related quality of life (HRQoL). To elucidate the burden of pruritus, we evaluated the relationship between pruritus severity, measured by the worst itch numerical rating scale (WI-NRS), and HRQoL utility outcomes, as assessed by EQ-5D.
METHODS: Pooled data from GLIMMER (NCT02966834), a placebo-controlled Phase 2b trial of linerixibat in patients with PBC and pruritus, and an observational, patient-reported outcome (PRO) validation study were used for the analyses. To examine the relationship and assess linearity between EQ-5D utility and WI-NRS, boxplots of UK-specific EQ-5D utility scores by WI-NRS as well as plots of residuals from univariate linear mixed models with WI-NRS as linear predictor, were evaluated. To account for potential non-linearity, a third degree polynomial model with spline functions including WI-NRS, WI-NRS2, and WI-NRS3 terms was fitted. This multivariate mixed model was further refined using stepwise selection algorithms and 3-fold cross validation.
RESULTS: The pooled dataset included 694 observations of EQ-5D utility scores and daily WI-NRS from 287 patients across multiple visits. The overall mean utility and WI-NRS were 0.72 and 4.51, respectively. Boxplots and residual plots indicated a non-linear worsening of EQ-5D utility scores with increasing WI-NRS scores. The EQ-5D utility model including all third degree polynomial spline functions of WI-NRS indicated potential overfitting, with all WI-NRS degree terms being non-significant; the model with only WI-NRS3 as predictor was the best-fitting model based on the Akaike information criterion.
CONCLUSIONS: The relationship between EQ-5D utility and WI-NRS was not linear, based on the pooled data from the GLIMMER and PRO validation studies. The relationship highlighted that higher WI-NRS scores, indicating more severe pruritus, have an increasingly negative impact on HRQoL. Funding: GSK (201000, 212144).
METHODS: Pooled data from GLIMMER (NCT02966834), a placebo-controlled Phase 2b trial of linerixibat in patients with PBC and pruritus, and an observational, patient-reported outcome (PRO) validation study were used for the analyses. To examine the relationship and assess linearity between EQ-5D utility and WI-NRS, boxplots of UK-specific EQ-5D utility scores by WI-NRS as well as plots of residuals from univariate linear mixed models with WI-NRS as linear predictor, were evaluated. To account for potential non-linearity, a third degree polynomial model with spline functions including WI-NRS, WI-NRS2, and WI-NRS3 terms was fitted. This multivariate mixed model was further refined using stepwise selection algorithms and 3-fold cross validation.
RESULTS: The pooled dataset included 694 observations of EQ-5D utility scores and daily WI-NRS from 287 patients across multiple visits. The overall mean utility and WI-NRS were 0.72 and 4.51, respectively. Boxplots and residual plots indicated a non-linear worsening of EQ-5D utility scores with increasing WI-NRS scores. The EQ-5D utility model including all third degree polynomial spline functions of WI-NRS indicated potential overfitting, with all WI-NRS degree terms being non-significant; the model with only WI-NRS3 as predictor was the best-fitting model based on the Akaike information criterion.
CONCLUSIONS: The relationship between EQ-5D utility and WI-NRS was not linear, based on the pooled data from the GLIMMER and PRO validation studies. The relationship highlighted that higher WI-NRS scores, indicating more severe pruritus, have an increasingly negative impact on HRQoL. Funding: GSK (201000, 212144).
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PCR78
Topic
Patient-Centered Research
Topic Subcategory
Instrument Development, Validation, & Translation
Disease
Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)