Pruritus Linked to Depression, Sleep Interference in PBC, Negatively Impacting HRQoL

Pruritus is associated with impaired health-related quality of life (HRQoL) in patients with primary biliary cholangitis (PBC), according to findings from a recent study.1

Leveraging patient-reported outcome data from the phase 2b GLIMMER study of the ileal bile acid transporter (IBAT) inhibitor linerixibat in patients with PBC and pruritus, the study found patients with severe pruritus at baseline had worse HRQoL along with greater rates of depression and sleep interference than those with mild/moderate pruritus.1

Historically, patients with PBC have had limited treatment options, starting with ursodeoxycholic acid (UDCA) and later expanding to include obeticholic acid (Ocaliva) as a second-line option for patients who did not respond to or could not tolerate UDCA. In 2024, the field saw the addition of 2 new second-line treatment options: elafibranor (Iqirvo) and seladelpar (Livdelzi).2,3 Despite the introduction of more treatments for patients, current PBC therapies primarily target the underlying disease and do not effectively address pruritus, a common and debilitating symptom affecting many patients with PBC.2

“Appreciation of the true impact of pruritus on HRQoL and the potential link between pruritus, sleep, and mental health have not been systematically explored,” Andreas Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, and colleagues wrote.1 “Understanding patients’ HRQoL is a critical part of providing optimized care. To better meet patient needs, we need to fully understand and better communicate the pervasive impact of pruritus in PBC.”

To characterize the impact of pruritus in PBC, investigators examined data from the multicenter, randomized, double-blind, phase 2b, dose-finding GLIMMER study of linerixibat, the largest investigational trial of cholestatic pruritus in PBC to date and the first to collect in-depth data at baseline regarding how pruritus impacts patients, including patient-reported measures of HRQoL.1

The study enrolled 147 adult patients with PBC and moderate to severe cholestatic pruritus. On day 1 of the study, patients entered an initial 4-week, single-blind, placebo run-in period to establish baseline symptoms.1

Pruritus severity was scored on a 0–10-point NRS and used to derive a weekly itch score to subdivide patients into pruritus severity subgroups at baseline following the placebo run-in. On this basis, 24% had mild pruritus, defined as NRS ≥3 to <4; 52% had moderate pruritus, defined as NRS ≥4 to <7; and 24% had severe pruritus, defined as NRS ≥7 to 10.1

Among the GLIMMER cohort, the majority of patients were female (94%) with a mean age of 55.8 (Standard deviation [SD], 11.0) years.1

Their health status was evaluated using the EQ-5D-5L health domains and utility index assessed on day 1, baseline, and week 16.1

Additionally, patients used the NRS to record the impact of pruritus on their sleep each morning. Investigators calculated a weekly sleep interference score using the mean of daily sleep interference scores over the 7 days before each visit. An NRS of <4 was considered no/mild sleep interference, ≥4 to <7 moderate, and ≥7 to 10 severe.1

Depression was assessed using the Beck Depression Inventory Second Edition at screening, baseline, and week 16. A total of 0–13 was considered no/minimal depression, 14–19 mild, 20–28 moderate, and 29–63 severe.1

At baseline, 146 patients provided EQ-5D-5L responses, with mean utility values of 0.69 (SD, 0.23). Investigators noted values were similar for patients with mild and moderate pruritus (0.75; SD, 0.17 and 0.76; SD, 0.17, respectively) but lower for patients with severe pruritus (0.49; SD, 0.28).1

At baseline, 52% of patients reported problems doing their usual activities, 75% reported some level of pain or discomfort, and 63% reported some level of anxiety or depression. Across all domains, patients with severe pruritus at baseline were more impacted than patients with mild or moderate pruritus.1

Among patients with severe pruritus, 31% had severe depression, versus 9% and 3% of those with mild and moderate pruritus, respectively. In patients with severe pruritus, investigators noted health utility scores were further decreased with any degree of depression.1

Additionally, they pointed out 54% of patients with severe pruritus reported severe sleep interference. Of note, all patients with mild pruritus reported having no/mild sleep interference. Like depression, health utility scores decreased with increasing degrees of sleep interference.1

For each 1-point improvement in NRS for pruritus between baseline and week 16, mean EQ-5D-5L utility scores improved.1

“We believe that this unique and comprehensive study provides important insights into the true nature and extent of the impact of pruritus in PBC and identifies important considerations for clinical practice,” investigators concluded.1

References

1. Smith HT, Das S, Fettiplace J, et al. Pervasive role of pruritus in impaired quality of life in patients with primary biliary cholangitis: Data from the GLIMMER study. Hepatol Commun. doi:10.1097/HC9.0000000000000635
2. Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed February 21, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc
3. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed February 21, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis
4. Brooks A. Marlyn Mayo, MD: Improving Pruritus Management in PBC Care. HCPLive. December 10, 2024. Accessed February 21, 2025. https://www.hcplive.com/view/marlyn-mayo-md-improving-pruritus-management-pbc-care