Insufficient control of cholestatic pruritus in primary biliary cholangitis (PBC) with current therapies: baseline data from the ongoing Phase 3 GLISTEN (Global Linerixibat Itch STudy of Efficacy and safety iN PBC) trial
Bibliographic record
Abstract
Background: Cholestatic pruritus is common in PBC, negatively impacts quality of life and efficacy of current therapies is limited. Linerixibat, an oral ileal bile acid transporter inhibitor, is currently in development for the treatment of pruritus in PBC. Here, we report baseline (BL) characteristics and pruritus treatment history in GLISTEN to characterize unmet patients’ needs. Methods: GLISTEN (NCT04950127) is an ongoing Phase 3, placebo-controlled study in adults with PBC and moderate–severe pruritus. Pruritus severity is assessed using a worst itch 0–10 numerical rating scale (NRS). Participants are either treatment-naïve, have received prior therapy or continue stable concomitant therapies for pruritus. A preliminary analysis of BL characteristics is presented. Results: Data from 227 participants were included. At BL, 42% had moderate pruritus (NRS 4-6), 58% severe (NRS≥7); 51% had alkaline phosphatase levels<1.67x upper limit of normal. The most common prior therapies for pruritus were antihistamines, bile acid binding resins, rifampin, and fibrates. Where specified, main reasons for stopping these treatments included lack of efficacy (83%, 55%, 69%, and 13%, respectively) and lack of tolerability (9%, 45%, 38%, and 88%, respectively). In total, 42% of participants were receiving concomitant therapy that may reduce pruritus, including 22% receiving fibrates. Conclusion: Prior use of bile acid binding resins was low in the GLISTEN population despite its first-line position in treatment guidelines. Regardless of the use of multiple “off label” therapies, participants had evidence of ongoing moderate–severe pruritus, underscoring the unmet need for a targeted therapy for pruritus in PBC. Publication History Article published online: 20 January 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".