PTU-009 Long-term effects of obeticholic acid in patients with primary biliary cholangitis on inflammatory markers
Bibliographic record
Abstract
Introduction Obeticholic Acid (OCA) is a potent and selective farnesoid X receptor agonist approved for the treatment of primary biliary cholangitis (PBC). PBC is a chronic liver disease characterized by the immune mediated destruction of bile ducts resulting in cholestasis, cirrhosis and liver failure. The POISE study was a randomized, placebo-controlled phase 3 study investigating daily OCA 5–10 mg in PBC patients with an ongoing open label extension (OLE). The purpose of this analysis was to assess the long-term effects of OCA on key markers of liver damage and inflammation. Methods Patients enrolled in the double-blind phase had an inadequate response to UDCA or were intolerant of UDCA. Patients were randomized to placebo, OCA 5–10 mg, or OCA 10 mg. Upon completion of the 12-month double-blind phase, 198 patients enrolled in the OLE and received OCA. For this analysis, patients were pooled and assessed from the time of first dose of OCA. Data are shown through 48 months of OCA exposure, for patients randomized to placebo in the double-blind phase, only 36 months of data are included. Results At baseline (N=198), patients were 92% female, mean age was 55 years, PBC disease duration was 9 years, and 93% received UDCA (mean dose: 16 mg/kg/day). As observed in the table, there were sustained and significant reductions in immunoglobulins (Ig) A, G and M throughout 48 months of OCA treatment. In addition, significant reductions were observed in tumor necrosis factor (TNF)-α, c-reactive protein (CRP), and cleaved cytokeratin (CK)-18 throughout the duration of the OLE. No clinically meaningful changes were observed with transforming growth factor (TGF)-β and interleukin (IL)-12, both remained within the normal range. Conclusions These results demonstrate that OCA has a durable anti-inflammatory effect in patients with PBC as observed by reductions on key markers of apoptosis (TNF-α and CK-18) and inflammation (CRP). Furthermore, a sustained reduction is observed in IgM, which is classically elevated in PBC patients. The clinical significance of OCA mediated reductions in IgA and IgG continues to remain unknown.
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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 | 0.000 | 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 | 0.000 | 0.000 |
| 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".