Gelhorn Heather, Currie Brooke M, Bushnell Donald M, Martin Mona L, Fofana Fatoumata, Karn Hayley, Mayo Marlyn J, Jones David E, McLaughlin Megan M, von Maltzahn Robyn
Evidera|PPD, Wilmington, NC, USA.
GSK, Collegeville, PA, USA.
Orphanet J Rare Dis. 2025 Jul 31;20(1):390. doi: 10.1186/s13023-025-03798-x.
Cholestatic pruritus is common in primary biliary cholangitis (PBC), often leading to sleep disturbances and substantially impairing health-related quality of life (HRQoL). Fatigue, also frequent in PBC, can be exacerbated by sleep interference due to nighttime pruritus. Quantitative numerical rating scales (NRS) are appropriate for assessing unidimensional patient-reported outcome (PRO) concepts and are easily interpreted. The PBC-40 is a disease-specific, patient-derived 40-item tool that assesses HRQoL in patients with PBC. To assess pruritus severity in clinical trials, rigorous validation of PROs in the target patient population is required. This study aimed to validate the NRS items for worst itch (WI-NRS), pruritus-related sleep interference (Sleep Interference NRS), and fatigue (Fatigue NRS), plus the PBC-40 (modified with a 7-day recall), among patients with PBC and pruritus.
Data were analyzed from the Phase 2b GLIMMER trial (NCT02966834) of linerixibat and a separate observational study in patients with PBC and pruritus. Pruritus severity was assessed using the 0-10 WI-NRS. Psychometric properties of the WI-NRS, Sleep Interference NRS, Fatigue NRS, and PBC-40 (7-day recall) were evaluated. Additional PRO data were used to support validation analyses. Multiple psychometric methods were used to validate the NRS items and PBC-40 (7-day recall).
Data for 288 patients (n=147 GLIMMER; n=141 observational study) with PBC experiencing pruritus were included. The internal consistency of PBC-40 (7-day recall) was acceptable to excellent and confirmatory factor analysis confirmed its domain structure. All PBC-40 domains showed acceptable test-retest reliability (intraclass correlation coefficients [ICCs]: 0.72-0.90). The WI-NRS showed acceptable test-retest reliability (ICCs: 0.73-0.81 [GLIMMER]; ICC: 0.78 [observational study]). Test-retest reliability was also acceptable for the Sleep Interference (ICC: 0.85 [GLIMMER]; ICC: 0.77 [observational study]) and Fatigue (ICC: 0.88 [GLIMMER]; ICC: 0.78 [observational study]) NRS items. Convergent, discriminant, and known-groups validity were confirmed for all three NRS items and the PBC-40. Additionally, the NRS and PBC-40 Itch domain demonstrated responsiveness by reflecting change in other PROs over time.
The data support the psychometric reliability, validity, and responsiveness of WI-NRS, pruritus-related Sleep Interference NRS, and Fatigue NRS, and PBC-40 (7-day recall) in patients with PBC experiencing pruritus.
胆汁淤积性瘙痒在原发性胆汁性胆管炎（PBC）中很常见，常导致睡眠障碍，并严重损害健康相关生活质量（HRQoL）。疲劳在PBC中也很常见，夜间瘙痒引起的睡眠干扰会加剧疲劳。定量数字评定量表（NRS）适用于评估患者报告的单维度结局（PRO）概念，且易于解释。PBC-40是一种针对疾病、源自患者的40项工具，用于评估PBC患者的HRQoL。为了在临床试验中评估瘙痒严重程度，需要在目标患者群体中对PRO进行严格验证。本研究旨在验证PBC合并瘙痒患者中最严重瘙痒（WI-NRS）、瘙痒相关睡眠干扰（睡眠干扰NRS）、疲劳（疲劳NRS）的NRS条目，以及PBC-40（采用7天回忆法修改）。
分析了来自linixibat的2b期GLIMMER试验（NCT02966834）以及一项针对PBC合并瘙痒患者的单独观察性研究的数据。使用0至10的WI-NRS评估瘙痒严重程度。评估了WI-NRS、睡眠干扰NRS、疲劳NRS和PBC-40（7天回忆法）的心理测量学特性。使用额外的PRO数据来支持验证分析。采用多种心理测量方法来验证NRS条目和PBC-40（7天回忆法）。
纳入了288例经历瘙痒的PBC患者的数据（n = 147例来自GLIMMER试验；n = 141例来自观察性研究）。PBC-40（7天回忆法）的内部一致性良好至优秀，验证性因子分析证实了其领域结构。所有PBC-40领域均显示出可接受的重测信度（组内相关系数[ICC]：0.72 - 0.90）。WI-NRS显示出可接受的重测信度（ICC：0.73 - 0.81[GLIMMER试验]；ICC：0.78[观察性研究]）。睡眠干扰（ICC：0.85[GLIMMER试验]；ICC：0.77[观察性研究]）和疲劳（ICC：0.88[GLIMMER试验]；ICC：0.78[观察性研究]）NRS条目的重测信度也可接受。所有三个NRS条目和PBC-40均证实了收敛效度、区分效度和已知群组效度。此外，NRS和PBC-40瘙痒领域通过反映其他PRO随时间的变化显示出反应性。
数据支持WI-NRS、瘙痒相关睡眠干扰NRS、疲劳NRS以及PBC-40（7天回忆法）在经历瘙痒的PBC患者中的心理测量学可靠性、效度和反应性。
