Pervasive role of pruritus in impaired quality of life in patients with primary biliary cholangitis: Data from the GLIMMER study

Helen T Smith; Sugato Das; James Fettiplace; Robyn von Maltzahn; Philip J F Troke; Megan M McLaughlin; David E Jones; Andreas E Kremer

doi:10.1097/HC9.0000000000000635

Pervasive role of pruritus in impaired quality of life in patients with primary biliary cholangitis: Data from the GLIMMER study

Hepatol Commun. 2025 Feb 19;9(3):e0635. doi: 10.1097/HC9.0000000000000635. eCollection 2025 Mar 1.

Authors

Helen T Smith¹, Sugato Das², James Fettiplace^{3

4}, Robyn von Maltzahn⁵, Philip J F Troke⁶, Megan M McLaughlin⁷, David E Jones⁸, Andreas E Kremer⁹

Affiliations

¹ Value Evidence, GSK, London, UK.
² Development Biostatistics, GSK, Hyderabad, India.
³ Clinical Development, GSK, London, UK.
⁴ Affiliation at the time of manuscript preparation.
⁵ Patient Centred Outcomes, GSK, London, UK.
⁶ Hepatology Global Medical Affairs, GSK, London, UK.
⁷ Development Medicine, Development Leaders, GSK, Collegeville, PA, USA.
⁸ NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle, UK.
⁹ Department of Gastroenterology and Hepatology, University of Zürich, Zürich, Switzerland.

Abstract

Background: Pruritus affects up to 80% of patients with primary biliary cholangitis (PBC) and reduces health-related quality of life (HRQoL). GLIMMER (NCT02966834) was a randomized, placebo-controlled phase IIb study of linerixibat in patients with PBC and pruritus. Using patient-reported outcome data from GLIMMER, we characterize the impact of pruritus in PBC.

Methods: To objectively assess HRQoL impact, EQ-5D-5L data from GLIMMER (0-1 scale; 0 = death, 1 = perfect health) were analyzed post-hoc across pruritus severities. Inter-relationships between pruritus severity (0-10 numerical rating scale [NRS]), depression (Beck Depression Inventory-II, post-hoc), and sleep interference (0-10 NRS) and their impact on HRQoL were explored.

Results: In patients with PBC (n = 147), severe pruritus was associated with worse HRQoL. EQ-5D-5L scores were lower in those with severe pruritus (≥7-10 NRS) versus mild/moderate pruritus (mean [SD]: 0.49 [0.28] and 0.75 [0.17]/0.76 [0.17], respectively). Among patients with severe pruritus, 31% had severe depression, versus 9/3% with mild/moderate pruritus. Patients with both severe pruritus and depression had a mean EQ-5D-5L score of 0.30. In those with severe pruritus, 54% reported severe sleep interference. Improvements in pruritus were accompanied by stepwise improvements in EQ-5D-5L scores.

Conclusions: This analysis of patients in the largest investigational trial of cholestatic pruritus to date shows a clear association between pruritus and impaired HRQoL. Patients with severe pruritus had HRQoL comparable to patients with severe Parkinson's disease. Severe pruritus alongside depression was associated with extremely poor HRQoL, indicating the importance of evaluating itch and managing depression. Sleep interference appears to be a major cofactor for reduced HRQoL. For each 1-point improvement in NRS HRQoL improved, clinicians should offer appropriate and timely intervention.

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial

MeSH terms

Adult
Aged
Depression / etiology
Female
Humans
Liver Cirrhosis, Biliary* / complications
Liver Cirrhosis, Biliary* / drug therapy
Liver Cirrhosis, Biliary* / psychology
Male
Methylamines
Middle Aged
Patient Reported Outcome Measures
Pruritus* / drug therapy
Pruritus* / etiology
Pruritus* / psychology
Quality of Life*
Severity of Illness Index
Thiazepines

Substances

3-((((3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl)methyl)amino)pentanedioic acid
Methylamines
Thiazepines