Seladelpar treatment of patients with primary biliary cholangitis improves the GLOBE score and predicts improved transplant-free survival
Bibliographic record
Abstract
Introduction: The GLOBE score is a validated risk assessment tool used to estimate transplant-free survival (TFS) in patients (pts) with primary biliary cholangitis (PBC). Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in pts who have an inadequate response to UDCA, or as a monotherapy in pts unable to tolerate UDCA. Objectives: This study evaluated the change in GLOBE score in pts with PBC on SEL from the placebo (PBO)-controlled Phase 3 RESPONSE (NCT04620733) trial and the subsequent open-label extension (ASSURE; NCT03301506). Methodology: Pts with PBC who received UDCA for≥12 months (M) or were intolerant to UDCA and had alkaline phosphatase (ALP)≥1.67×the upper limit of normal (ULN) and total bilirubin (TB)≤2×ULN were enrolled in RESPONSE and randomised 2:1 to receive daily SEL 10 mg or PBO. After 1 year (Y), pts were eligible for ASSURE, in which pts on PBO could switch to SEL (crossover) and pts on SEL continued treatment (continuous). Change in GLOBE score, predicted TFS, and the contributions of ALP, TB, albumin, and platelets to changes in GLOBE score were evaluated. Results: 193 pts were enrolled; 95% were female. At baseline (BL), mean (SD) age and duration of PBC were 57 (9.7) and 8 (6.6) years, with mean (SD) ALP: 314 (120.9) U/L; TB: 0.76 (0.31) mg/dL; albumin: 4.1 (0.26) g/dL; platelets: 242 (80.6)×10 3 /uL; and GLOBE score: 0.32 (0.68). Mean (SD) changes in GLOBE score from BL at 3M and 1Y for pts on SEL were−0.38 (0.21) and−0.34 (0.39), respectively, vs−0.07 (0.28) and−0.01 (0.32) for pts on PBO. At 2Y, GLOBE score changes were−0.39 (0.33) and−0.42 (0.50) for pts on continuous or crossover SEL, respectively. For pts on SEL, the greatest changes in GLOBE score were attributable to the ALP component (3M,−0.20; 1Y,−0.21; 2Y,−0.19), followed by the TB component (3M,−0.11; 1Y,−0.09; 2Y,−0.13). SEL treatment for 3M, 1Y, and 2Y led to predicted changes in TFS with hazard ratios (HRs [95% CIs]) of 0.7 (0.7–0.7), 0.8 (0.7–0.9), and 0.7 (0.6–0.8) compared with BL, respectively; HRs (95% CIs) for pts on PBO at 3M and 1Y were 1.0 (0.9–1.0) and 1.0 (1.0–1.1). At 2Y, pts on crossover SEL had similar results to those on continuous SEL. Conclusion: SEL treatment resulted in an early decrease in GLOBE score for pts with PBC, which was maintained over 2Y and was associated with improved predicted TFS. Publication History Article published online: 04 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".