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Record W4403391574 · doi:10.1136/gutjnl-2024-basl.34

P23 Efficacy of elafibranor in primary biliary cholangitis: results from the variable double-blind period of ELATIVE®, a randomised, placebo-controlled phase III trial

2024· article· en· W4403391574 on OpenAlexaff
Christopher L. Bowlus, Kris V. Kowdley, Cynthia Levy, Ulus Salih Akarca, Mário Reis Álvares‐da‐Silva, Pietro Andreoné, Marco Arrese, Christophe Corpechot, Sven Francque, Michael A. Heneghan, Pietro Invernizzi, David Jones, Frederik C. Kruger, Eric Lawitz, Marlyn J. Mayo, Mitchell Shiffman, Mark G. Swain, José Miguel Valera, Victor Vargas Blasco, John M. Vierling, Alejandra Villamil, Julie Dietrich, Daniel Shu, Nuno Antunes, Marwan Sleiman, Nathan Touati, Jörn M. Schattenberg

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicLiver Diseases and Immunity
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsPlaceboDouble blindMedicineInternal medicineGastroenterologyAlternative medicine

Abstract

fetched live from OpenAlex

Introduction Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease characterised by the destruction of interlobular bile ducts, resulting in cholestasis and biliary fibrosis. Elafibranor, a dual peroxisome proliferator-activated receptor-alpha/delta agonist, significantly improved prognostic biomarkers of cholestasis at Week 52 in patients with PBC in the phase III ELATIVE® trial.1 Here, we report the efficacy outcomes from ELATIVE® beyond Week 52. Methods In ELATIVE® (NCT04526665), patients with PBC and an inadequate response or intolerance to ursodeoxycholic acid, with alkaline phosphatase (ALP) ≥1.67 x upper limit of normal (ULN) and total bilirubin (TB) ≤2 x ULN, were randomised 2:1 to elafibranor 80mg or placebo once daily for ≥52 weeks. Patients continued their assigned regimen after Week 52 until all patients had completed the Week 52 visit or for a maximum of 104 weeks, whichever came first. We report efficacy outcomes beyond Week 52, during the variable double-blind period, with a focus on Week 78. Biochemical response, the primary endpoint at Week 52, was defined as ALP <1.67 x ULN, with ≥ 15% reduction from baseline, and TB ≤ULN. Data reported here are descriptive for patients with available data at Week 78. Results Among 161 randomised patients, 96/108 (89%) receiving elafibranor and 47/53 (89%) receiving placebo completed treatment to Week 52 (efficacy data reported previously1); 30/108 (28%) patients receiving elafibranor and 13/53 (25%) receiving placebo attended a Week 78 visit. At Week 78, the biochemical response endpoint was achieved in 19/27 (70%) patients receiving elafibranor compared with 0/13 (0%) patients receiving placebo. ALP normalisation occurred in 5/27 (19%) patients receiving elafibranor compared with 0/13 (0%) patients receiving placebo. Mean change from baseline to Week 78 in ALP was −135.3U/L in patients receiving elafibranor (n=26) versus 31.0U/L in patients receiving placebo (n=12). Mean change from baseline to Week 78 in TB was −1.2μmol/L in patients receiving elafibranor (n=25), while patients receiving placebo had a worsening of mean TB levels with an increase of 3.1μmol/L (n=12). Mean change from baseline to Week 78 in gamma glutamyl transferase (GGT) was −56.3U/L in patients receiving elafibranor (n=26) versus −10.3U/L in patients receiving placebo (n=12). Discussion Longer term treatment with elafibranor in patients with PBC through 78 weeks improved prognostic biomarkers of cholestasis beyond the positive efficacy outcomes previously reported through Week 52.1 Reference Kowdley KV. N Engl J Med. 2024;390(9):795–805. Study sponsor: GENFIT; secondary analysis and publication sponsor: Ipsen.

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 imitation

Not 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.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.025

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0080.001

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.

Opus teacher head0.029
GPT teacher head0.304
Teacher spread0.276 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

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".

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Citations0
Published2024
Admission routes1
Has abstractyes

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