Effect of Obeticholic Acid Treatment in Patients With Primary Biliary Cholangitis on Categorical Shifts in GLOBE Score
Bibliographic record
Abstract
Introduction: The Global PBC Study Group have developed and validated the GLOBE score: a prognostic algorithm (calculated from: age, ALP, total bilirubin, platelets and albumin) to predict risk of liver transplantation and all-cause mortality (http://www.globalpbc.com). A GLOBE score ≤0.3 is associated with a liver transplant-free survival similar to that of a sex and age matched normal population, whereas a GLOBE score >0.3 is associated with significantly diminished liver transplant-free survival. POISE was a placebo-controlled, double-blind, 12-month Phase 3 study which assessed the efficacy of daily 5-10 mg obeticholic acid (OCA) in patients with PBC. The aim of this analysis was to use data from POISE trial to assess if OCA treatment had an effect on categorical shifts in the GLOBE score. Methods: POISE inclusion criteria: PBC diagnosis, ALP ≥1.67x ULN and/or total bilirubin >ULN to < 2x ULN, stable UDCA dose or unable to tolerate UDCA. 216 patients were randomized and dosed with Placebo (PBO, n=73), OCA 5-10 mg (n=70; titration from daily 5 mg to 10 mg at month 6 based on response or tolerability), or OCA 10 mg (n=73). The GLOBE score was calculated at baseline and month 12 to assess disease progression. Results: At baseline there were a similar number of patients across treatment groups who had a GLOBE score above or below 0.3. After 12 months of treatment, patients receiving OCA 5-10 mg (27%, p < 0.05) were significantly more likely to shift from above to below a GLOBE score of 0.3, as compared to PBO (6%). Additionally, after 12 months of treatment, more PBO patients (33%) compared to OCA-treated patients (OCA 5-10 mg: 13%, p= 0.06; OCA 10 mg: 3%, p < 0.01) progressed from a baseline GLOBE score below 0.3 to a GLOBE score above 0.3. Conclusion: OCA treatment resulted in a significantly greater number of patients achieving a GLOBE score ≤0.3, associated with survival that is similar to age and sex matched individuals as compared to PBO treatment. Also, fewer patients progressed to a GLOBE score >0.3, associated with diminished survival. These changes indicate a potential effect of OCA after only 12 months of treatment to delay disease progression in PBC patients who are insufficiently responding to UDCA; however, further evaluation is required. A Phase 3 study evaluating clinical outcomes with OCA in patients with PBC (COBALT) is ongoing to confirm the clinical benefit of OCA and may be used to test the utility of the GLOBE score with OCA.Figure
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".