SEARCHCOHORTpediatrics, gastroenterology

cohort·pediatrics, gastroenterology, clinical trial, observational study·PMC10653287

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor

Hepatology (Baltimore, Md.) · 10 authors, 8 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This pooled analysis of 76 Alagille syndrome patients from three clinical trials found that a meaningful reduction in pruritus and lower week 48 bilirubin and serum bile acid levels were associated with a higher probability of surviving 6 years without liver transplant, biliary diversion, hepatic decompensation, or death.

Full summary

869 CHARS

This study analyzed data from 76 children with Alagille syndrome who were treated with maralixibat for a median of 4.7 years across three clinical trials. The analysis aimed to identify predictors of 6-year event-free survival (EFS) and transplant-free survival (TFS). Using Cox proportional hazard models, the researchers found that a greater than 1-point reduction in pruritus score (ItchRO[Obs]) from baseline to week 48, a week 48 total bilirubin less than 6.5 mg/dL, and a week 48 serum bile acid level less than 200 µmol/L were significantly associated with improved EFS. For example, 88% of patients with the pruritus reduction achieved EFS compared to 57% without it. Similar improvements were seen for TFS. The findings suggest these clinical and biochemical markers may be useful for monitoring disease progression and treatment response in Alagille syndrome.

STUDY TYPE

cohort

SPECIALTY

pediatrics

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10653287

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor

Hepatology (Baltimore, Md.)

READ THE FULL PAPER

ABSTRACT

Background and Aims: Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor. Approach and Results: We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up. Event-free survival was defined as the absence of LT, surgical biliary diversion, hepatic decompensation, or death; transplant-free survival was the absence of LT or death. Forty-three potential predictors were evaluated, including age, pruritus (ItchRO[Obs] 0–4 scale), biochemistries, platelets, and serum bile acids. Harrell’s concordance statistic assessed goodness-of-fit, and then, Cox proportional hazard models confirmed the statistical significance of the predictors identified. A further analysis was performed to identify cutoffs using a grid search. Seventy-six individuals met the criteria of receiving MRX for ≥48 weeks with laboratory values available at week 48 (W48). The median duration of MRX was 4.7 years (IQR: 1.6–5.8); 16 had events (10 LT, 3 decompensation, 2 death, and 1 surgical biliary diversion). The 6-year event-free survival improved with a clinically meaningful >1-point ItchRO(Obs) reduction from baseline to W48 (88% vs. 57%; p = 0.005), W48 bilirubin < 6.5 mg/dL (90% vs. 43%; p < 0.0001), and W48 serum bile acid < 200 µmol/L (85% vs. 49%; p = 0.001). These parameters were also predictive of 6-year transplant-free survival. Conclusions: Improvement in pruritus by 48 weeks, and lower W48 bilirubin and serum bile acid levels were associated with fewer events. These data may help identify potential markers of disease progression for ALGS patients treated with MRX.

CITATION EXPORT

Ronald J. Sokol, Emmanuel M. Gonzales, Binita M. Kamath et al.. Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor. Hepatology (Baltimore, Md.). (2023). https://doi.org/10.1097/HEP.0000000000000502

AUTHORS

10 · 8 CENTRES

Ronald J. Sokol, Emmanuel M. Gonzales, Binita M. Kamath, Alastair Baker, Pamela Vig, Douglas B. Mogul, Will Garner, Bettina E. Hansen, Emmanuel Jacquemin, Richard J. Thompson

1Section of Pediatric Gastroenterology, Hepatology and Nutrition and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado, USA
2Department of Pediatric Hepatology and Liver Transplantation, National reference center for biliary atresia and genetic cholestasis (AVB-CG), FSMR FILFOIE, ERN RARE-LIVER, AP-HP, Université Paris-Saclay, Bicêtre Hospital, Le Kremlin-Bicêtre, France
3Department of Pediatric Hepatology and Liver Transplantation, Inserm UMR_S 1193, Université Paris-Saclay, FHU Hepatinov, Orsay, France
4Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada
5Pediatric Liver Department, Pediatric Liver Centre, King’s College Hospital, London, UK
6Department of Scientific and Medical Affairs, Mirum Pharmaceuticals Inc., Foster City, California, USA
7Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
8Department of Inflammation Biology, Institute of Liver Studies, King’s College London, London, UK