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Clinical Trial
. 2024 Jun 12;8(1):60.
doi: 10.1186/s41687-024-00722-y.

Relationship between pruritus and sleep in participants with primary biliary cholangitis in the Phase 2b GLIMMER trial

Robyn von Maltzahn  1 , Marlyn J Mayo  2 , Helen T Smith  1 , April Thompson  3 , Sugato Das  4 , Andrea Ribeiro de Souza  5 , Edoardo Lisi  1 , Cynthia Levy  6 , Megan M McLaughlin  7 , David Jones  8
Affiliations
Clinical Trial

Relationship between pruritus and sleep in participants with primary biliary cholangitis in the Phase 2b GLIMMER trial

Robyn von Maltzahn et al. J Patient Rep Outcomes. .

Abstract

Background: Cholestatic pruritus and fatigue are debilitating conditions associated with primary biliary cholangitis (PBC) and can significantly impact patients' quality of life. Pruritus in PBC often worsens at night and patients frequently report sleep disturbance, which contributes to cognitive symptoms and fatigue. Linerixibat is an ileal bile acid transporter inhibitor in clinical development for the treatment of pruritus associated with PBC and was recently assessed versus placebo in the Phase 2b GLIMMER trial. This post-hoc analysis assesses the relationship between pruritus severity and sleep disturbance in participants of GLIMMER regardless of treatment group.

Methods: GLIMMER (NCT02966834), a multicenter, double-blind, randomized, placebo-controlled trial, recruited 147 patients with PBC and moderate-to-severe pruritus. Following 4 weeks single-blind placebo, patients (randomized 3:1) received linerixibat or placebo for 12 weeks (to Week 16). Participants graded their itch (twice daily) and its interference with sleep (once daily) in an electronic diary using a 0-10 numerical rating scale (NRS). Weekly and monthly itch scores were calculated as the mean of the worst daily itch score over the respective time period. At study visits, participants completed the 5-D itch scale and the PBC-40 quality of life questionnaire, both of which contain an item specific to itch-related sleep disturbance. The impact of pruritus on sleep was assessed post hoc through correlations between the changes in NRS, 5-D itch, and PBC-40.

Results: Strong correlations were found between change from baseline in weekly itch and sleep NRS scores (r = 0.88 [95% confidence interval (CI): 0.83; 0.91]) at the end of treatment (Week 16), as well as in monthly itch and sleep NRS scores (r = 0.84 [95% CI: 0.80; 0.87]). Patients with improved weekly pruritus score severity category demonstrated reduced perceived sleep interference on average. Itch responders (≥2-point improvement in weekly itch score from baseline) displayed larger improvements in weekly sleep NRS score, 5-D itch, and PBC-40 sleep items, than itch non-responders (<2-point improvement).

Conclusions: A strong correlation exists between changes in pruritus severity and sleep interference in patients with PBC; pruritus reduction could generate concomitant improvement in sleep.

Keywords: Cholestatic pruritus; Health-related quality of life; IBAT inhibitor; PBC; Primary biliary cholangitis; Sleep interference.

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Conflict of interest statement

RVM is an employee of GSK and holds GSK shares. MJM has received research support from CymaBay, GSK, Intercept, Mallinckrodt, Salix, and TARGET RWE; and has consulted for CymaBay, GSK, Mallinckrodt, Mirum, and TARGET RWE. HTS is an employee of GSK and holds GSK shares. AT was an employee of GSK at the time of the study and holds GSK shares. SD is an employee of GSK. ARdS is an employee of GSK and holds GSK shares. EL is an employee of GSK and holds GSK shares. CL is an ABIM committee member and an associate editor of Hepatology; has consulted for Calliditas, CymaBay, DISC Medicine, Gilead, GSK, Intercept, Mirum, Pliant, Target RWE, and Ipsen; has participated on advisory boards for Bausch, Cymabay, GSK, Ipsen, Intercept and Pliant; and has received research grants from Cara Therapeutics, CymaBay, Disc Medicine, Escient, Genfit, Calliditas, Gilead, GSK, HighTide, Intercept, Mirum, Pliant, Target RWE, Ipsen and Zydus. MMM is an employee of GSK and holds GSK shares. DJ has received grant funding or fees from Abbott, Falk, GSK, Intercept, Novartis, and Pfizer.

Figures

Fig. 1
Fig. 1
Correlation between change from baseline in weekly sleep and itch scores at Week 16. n = 135 patients. Pearson product-moment correlation was used. BID twice daily, CI confidence interval, QD once daily
Fig. 2
Fig. 2
Correlation of CFB in monthly sleep and itch scores at Week 16. N = 147 patients (intent-to-treat population). Bland–Altman repeated measures correlation. Each colored dot and corresponding line is associated with an individual patient. CFB change from baseline, CI confidence interval
Fig. 3
Fig. 3
Reduction in sleep interference by pruritus severity improvements from baseline at Week 16. n = 135 patients. Improvement by two severity categories corresponds to change in pruritus from severe to mild or moderate to none
Fig. 4
Fig. 4
Itch responders analysis: CFB in weekly sleep score (n = 135), 5-D itch (n = 134), and PBC-40 itch domain sleep item (n = 134). A weekly sleep score; B 5-D itch scale impact of itch on sleep (disability domain sleep item) and C PBC-40 itch domain sleep item 8, impact of itch on sleep. A patient was considered an itch responder if they had a weekly itch score improvement from baseline of at least 2 points on the itch NRS at Week 16. Changes from baseline in continuous endpoints by itch responder groups are presented as box plots with mean (diamond), median, interquartile range, minimum, maximum, and outliers plotted. CFB change from baseline, PBC-40 quality of life measure for primary biliary cholangitis, 5-D 5-dimension
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