Hansen, Bettina E. and Vandriel, Shannon M. and Vig, Pamela and Garner, Will and Mogul, Douglas B. and Loomes, Kathleen M. and Piccoli, David A. and Rand, Elizabeth B. and Jankowska, Irena and Czubkowski, Piotr and Gliwicz-Miedzinska, Dorota and Gonzales, Emmanuel M. and Jacquemin, Emmanuel and Bouligand, Jerome and D'Antiga, Lorenzo and Nicastro, Emanuele and Arnell, Henrik and Fischler, Bjorn and Sokal, Etienne and Demaret, Tanguy and Siew, Susan and Stormon, Michael and Karpen, Saul J. and Romero, Rene and Ebel, Noelle H. and Feinstein, Jeffrey A. and Roberts, Amin J. and Evans, Helen M. and Sundaram, Shikha S. and Chaidez, Alexander and Hardikar, Winita and Shankar, Sahana and Fischer, Ryan T. and Lacaille, Florence and Debray, Dominique and Lin, Henry C. and Jensen, M. Kyle and Jaramillo, Catalina and Karthikeyan, Palaniswamy and Indolfi, Giuseppe and Verkade, Henkjan J. and Larson-Nath, Catherine and Quiros-Tejeira, Ruben E. and Valentino, Pamela L. and Rogalidou, Maria and Dezsofi, Antal and Squires, James E. and Schwarz, Kathleen and Calvo, Pier Luigi and Bernabeu, Jesus Quintero and Zizzo, Andreanne N. and Nebbia, Gabriella and Bulut, Pinar and Santos-Silva, Ermelinda and Fawaz, Rima and Nastasio, Silvia and Karnsakul, Wikrom and Tamara, Maria Legarda and Busoms, Cristina Molera and Kelly, Deirdre A. and Sandahl, Thomas Damgaard and Jimenez-Rivera, Carolina and Banales, Jesus M. and Mujawar, Quais and Li, Li-Ting and She, Huiyu and Wang, Jian-She and Kim, Kyung Mo and Oh, Seak Hee and Sanchez, Maria Camila and Cavalieri, Maria Lorena and Lee, Way Seah and Hajinicolaou, Christina and Lertudomphonwanit, Chatmanee and Waisbourd-Zinman, Orith and Arikan, Cigdem and Alam, Seema and Carvalho, Elisa and Melere, Melina and Eshun, John and Onal, Zerrin and Desai, Dev M. and Wiecek, Sabina and Pinto, Raquel Borges and Wolters, Victorien M. and Garcia, Jennifer and Beretta, Marisa and Kerkar, Nanda and Brecelj, Jernej and Rock, Nathalie and Lurz, Eberhard and Blondet, Niviann and Shah, Uzma and Thompson, Richard J. and Kamath, Binita M. and GALA, Global Alagille Alliance (2024) Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA. Hepatology, 79 (6). pp. 1279-1292. ISSN 0270-9139, DOI https://doi.org/10.1097/HEP.0000000000000727.
Full text not available from this repository.Abstract
Background and Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the Global ALagille Alliance (GALA) study. Approach and Results: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p < 0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. Conclusions:This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.
| Item Type: | Article |
|---|---|
| Funders: | Alagille Syndrome Alliance, Takeda Pharmaceutical Company Ltd, Albireo Pharma, Inc. |
| Uncontrolled Keywords: | Maralixibat-treated patients; Alagille syndrome; GALA |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Paediatrics Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 09 Dec 2024 03:47 |
| Last Modified: | 09 Dec 2024 03:47 |
| URI: | http://eprints.um.edu.my/id/eprint/47136 |
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