Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA

Event-free survival; Alagille syndrome

Detalhes bibliográficos
Autores: Hansen, Bettina, Vandriel, Shannon, Vig, Pamela, Garner, Will, Mogul, Douglas, Loomes, Kathleen, Quintero Bernabeu, Jesús
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/11490
Acesso em linha:https://hdl.handle.net/11351/11490
http://hdl.handle.net/11351/11490
Access Level:acceso abierto
Palavra-chave:Conductes biliars - Malalties - Tractament
Colèstasi
Avaluació de resultats (Assistència sanitària)
Àcids biliars
DISEASES::Digestive System Diseases::Biliary Tract Diseases::Bile Duct Diseases::Cholestasis::Cholestasis, Intrahepatic::Alagille Syndrome
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades de la vía biliar::enfermedades de los conductos biliares::colestasis::colestasis intrahepática::síndrome de Alagille
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
id ES_992fb137503d7204eb5c8a04b7ccf1aa
oai_identifier_str oai:recercat.cat:11351/11490
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
title Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
spellingShingle Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
Hansen, Bettina
Conductes biliars - Malalties - Tractament
Colèstasi
Avaluació de resultats (Assistència sanitària)
Àcids biliars
DISEASES::Digestive System Diseases::Biliary Tract Diseases::Bile Duct Diseases::Cholestasis::Cholestasis, Intrahepatic::Alagille Syndrome
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades de la vía biliar::enfermedades de los conductos biliares::colestasis::colestasis intrahepática::síndrome de Alagille
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
title_short Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
title_full Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
title_fullStr Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
title_full_unstemmed Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
title_sort Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA
dc.creator.none.fl_str_mv Hansen, Bettina
Vandriel, Shannon
Vig, Pamela
Garner, Will
Mogul, Douglas
Loomes, Kathleen
Quintero Bernabeu, Jesús
author Hansen, Bettina
author_facet Hansen, Bettina
Vandriel, Shannon
Vig, Pamela
Garner, Will
Mogul, Douglas
Loomes, Kathleen
Quintero Bernabeu, Jesús
author_role author
author2 Vandriel, Shannon
Vig, Pamela
Garner, Will
Mogul, Douglas
Loomes, Kathleen
Quintero Bernabeu, Jesús
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Hansen BE] Department of Hepatology, Toronto General Hospital University Health Network, Toronto, Ontario, Canada. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. [Vandriel SM] Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada. [Vig P, Garner W, Mogul DB] Department of Scientific and Medical Affairs, Mirum Pharmaceuticals, Inc., Foster City, California, USA. [Loomes KM] Department of Pathology and Laboratory Medicine, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. [Quintero J] Unitat de Gastroenterologia, Hepatologia, Suport Nutricional i Trasplantaments Hepàtics Pediàtrics, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Conductes biliars - Malalties - Tractament
Colèstasi
Avaluació de resultats (Assistència sanitària)
Àcids biliars
DISEASES::Digestive System Diseases::Biliary Tract Diseases::Bile Duct Diseases::Cholestasis::Cholestasis, Intrahepatic::Alagille Syndrome
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades de la vía biliar::enfermedades de los conductos biliares::colestasis::colestasis intrahepática::síndrome de Alagille
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
topic Conductes biliars - Malalties - Tractament
Colèstasi
Avaluació de resultats (Assistència sanitària)
Àcids biliars
DISEASES::Digestive System Diseases::Biliary Tract Diseases::Bile Duct Diseases::Cholestasis::Cholestasis, Intrahepatic::Alagille Syndrome
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades de la vía biliar::enfermedades de los conductos biliares::colestasis::colestasis intrahepática::síndrome de Alagille
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
description Event-free survival; Alagille syndrome
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/11490
http://hdl.handle.net/11351/11490
url https://hdl.handle.net/11351/11490
http://hdl.handle.net/11351/11490
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Hepatology;79(6)
https://doi.org/10.1097/HEP.0000000000000727
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Lippincott, Williams & Wilkins
publisher.none.fl_str_mv Lippincott, Williams & Wilkins
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALAHansen, BettinaVandriel, ShannonVig, PamelaGarner, WillMogul, DouglasLoomes, KathleenQuintero Bernabeu, JesúsConductes biliars - Malalties - TractamentColèstasiAvaluació de resultats (Assistència sanitària)Àcids biliarsDISEASES::Digestive System Diseases::Biliary Tract Diseases::Bile Duct Diseases::Cholestasis::Cholestasis, Intrahepatic::Alagille SyndromeOther subheadings::Other subheadings::Other subheadings::/drug therapyANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free SurvivalCHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and SaltsOther subheadings::Other subheadings::Other subheadings::/antagonists & inhibitorsENFERMEDADES::enfermedades del sistema digestivo::enfermedades de la vía biliar::enfermedades de los conductos biliares::colestasis::colestasis intrahepática::síndrome de AlagilleOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresiónCOMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliaresOtros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidoresEvent-free survival; Alagille syndromeSupervivencia libre de eventos; Síndrome de AlagilleSupervivència lliure d'esdeveniments; Síndrome d'AlagilleBackground 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.Funding for GALA was provided by the Alagille Syndrome Alliance, Mirum Pharmaceuticals, Inc., and Albireo Pharma, Inc., through unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation).Lippincott, Williams & WilkinsInstitut Català de la Salut[Hansen BE] Department of Hepatology, Toronto General Hospital University Health Network, Toronto, Ontario, Canada. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. [Vandriel SM] Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada. [Vig P, Garner W, Mogul DB] Department of Scientific and Medical Affairs, Mirum Pharmaceuticals, Inc., Foster City, California, USA. [Loomes KM] Department of Pathology and Laboratory Medicine, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. [Quintero J] Unitat de Gastroenterologia, Hepatologia, Suport Nutricional i Trasplantaments Hepàtics Pediàtrics, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, SpainVall d'Hebron Barcelona Hospital Campus2024202420232024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/11490http://hdl.handle.net/11351/11490Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésHepatology;79(6)https://doi.org/10.1097/HEP.0000000000000727Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/114902026-05-29T05:05:01Z
score 15,812429

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