OC29 Clinical benefits of maralixibat for patients with Alagille syndrome are durable through 7 years of treatment: data from the MERGE study
Bibliographic record
Abstract
Maralixibat (MRX), an ileal bile acid transport inhibitor (IBATi), is approved for the treatment of cholestatic pruritus in patients with Alagille Syndrome (ALGS) ≥2 months of age in Europe. Improvements in pruritus, serum bile acids (sBA), and height have been demonstrated from prior clinical trials including ICONIC, which followed participants up to 4 years, as well as IMAGO/IMAGINE and ITCH/IMAGINE-II, which reported outcomes to approximately 1.5 years. Participants from ICONIC, IMAGINE, and IMAGINE-II trials were invited to enroll in MERGE for additional long-term follow-up (LTFU); prior long-term survival outcomes (e.g., liver transplant, death) for this group have been previously reported. Here we report on efficacy in participants with additional LTFU from MERGE, including some participants that have received treatment for 7 years. All participants from ICONIC, IMAGINE and IMAGINE-II were included in the analysis. Impact of MRX was assessed for pruritus [ItchRO(Obs) 0–4 scale, with a ≥1-point reduction considered clinically meaningful], sBA, height and weight z-scores, ALT, total bilirubin (TB) and direct bilirubin (DB). Change from Baseline (CFB) was determined by comparing median (Q1, Q3) values from enrolment in the initial trial (i.e., ICONIC, IMAGO, or ITCH) to data from the visit in MERGE that best aligned with an annual visit. Data were analyzed for 86 participants at Baseline, with follow-up to 1 year for 76 participants, 4 years for 42 participants, and 7 years for 23 participants. Of the 86 participants, 84 had a genetic diagnosis of ALGS via the JAG1 mutation, 2 participants had a genetic diagnosis of ALGS via the NOTCH2 mutation, and 1 participant had an unidentified mutation. Baseline mean (SD) ItchRO(Obs) was 2.65 (0.75) and clinically meaningful reductions over time with CFB of -1.57 (-0.83, -2.14), -2.00 (-1.43, -2.56), and -2.14 (-1.43, -3.00) at 1 year, 4 years and 7 years, respectively. Likewise, Baseline sBA was 254 (207) µmol/L and decreased with CFB of -57 (8, -150) µmol/L, -62 (-32, -152) µmol/L, and -105 (-41, -266) µmol/L at 1 year, 4 years and 7 years. Improvement was observed in height, with Baseline z-score of -1.7 (1.27) and CFB of 0.1 (-0.1, 0.3), 0.3 (0.0, 1.0), and 0.7 (0.0, 1.2) at 1 year, 4 years and 7 years while weight z-scores were largely unchanged. Reductions in TB and DB were observed after treatment with maralixibat. No clinically meaningful changes in ALT or AST were observed with maralixibat treatment. There were no new safety signals. In this unmatched cohort, the benefit of MRX in ALGS patients, including both improvements in clinical outcomes and sBA, persist through 7 years of treatment. No new safety concerns were identified in the long-term.
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 | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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.
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".