O24 Durability of obeticholic acid response in PBC patients who did not achieve poise trial criteria
Bibliographic record
Abstract
Introduction In clinical studies and in clinical practice, response to primary biliary cholangitis (PBC) treatment has been assessed using dichotomous biochemical response criteria. Although achieving these criteria may be associated with improved clinical outcomes, the benefit in patients (pts) with an incomplete response to treatment may be underestimated. This analysis assessed the extent and durability of obeticholic acid (OCA) response in pts with PBC not achieving the dichotomous primary endpoint in the phase 3 POISE study through 72 months of OCA treatment. Methods Key inclusion criteria included PBC diagnosis, alkaline phosphatase (ALP) ≥1.67× upper limit of normal (ULN) and/or total bilirubin >ULN to <2× ULN, and on a stable dose of—or intolerant of—ursodeoxycholic acid (UDCA). During the 12-month double-blind (DB) phase, 216 pts were randomised to daily placebo, OCA 5–10 mg, or OCA 10 mg. This analysis pooled DB placebo (OCA baseline [BL] was open-label extension [OLE] day 0) and DB OCA pts to evaluate the efficacy and safety of up to 72 months of OCA treatment. Pts who achieved the POISE primary endpoint (ALP<1.67×ULN, with a ≥15% reduction from BL, and total bilirubin ≤ULN) 12 months from OCA BL were excluded. Values shown are mean (SD) unless otherwise specified. P values were based on paired t-tests. Results Of the 193 pts enrolled in the OLE, 107 (55%) did not achieve the POISE criteria after 12 months of OCA treatment. Pts were 93% female, 91% Caucasian, 56 (10) years old at BL, and 91% received UDCA (15 [4] mg/kg/day). At BL, ALP was 356 (138) U/L and total bilirubin was 13 (8) µmol/L (>ULN in 18 pts [17%]). Despite not achieving the POISE criteria after 12 months of OCA, a significant and durable reduction was observed in ALP (p<0.01 at all time points) through 72 months of treatment (figure 1). Total bilirubin levels remained stable and near BL values within the normal range through the duration of treatment. Throughout the 6-year study period, the most common adverse events were pruritus (92 pts [86%]) and fatigue (33 pts [31%]), consistent with previous reports from POISE and expected PBC symptoms. Conclusions Despite not achieving the POISE primary endpoint, these pts showed significant and sustained biochemical improvements.
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 | 0.005 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 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) | 0.004 | 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".