Surgical interruption of the Enterohepatic Circulation is Associated with an Increased Risk of Liver Transplantation or Death in Children with Alagille Syndrome

Surgical interruption of the Enterohepatic Circulation is Associated with an Increased Risk of Liver Transplantation or Death in Children with Alagille Syndrome Shannon M. Vandriel1 , Kathleen M. Loomes2 , David A. Piccoli2 , Elizabeth B. Rand2 , Li-Ting Li3 , Huiyu She3 , Jian-She Wang3 , Rima Fawaz4 , Silvia Nastasio5 , Henkjan J. Verkade6 , M. Kyle Jensen7 , Catalina Jaramillo7 , Nathalie Rock8 , Irena Jankowska9 , Piotr Czubkowski9 , Dorota Gliwicz-Miedzińska9 , Henry C. Lin10, Deirdre A. Kelly11, Jane Hartley11, Catherine Larson-Nath12, Florence Lacaille13, Dominique Debray14, Saul J. Karpen15, Rene Romero15, Cristina Molera Busoms16, Étienne Sokal17, Xavier Stéphenne17, Nehal M. El-Koofy18, Mohamed A. Elmonem19, Shikha S. Sundaram20, Alexander Chaidez20, Wikrom Karnsakul21 , Winita Hardikar22 , Sahana Shankar23 , Ruben E. Quiros-Tejeira24 , Seema Alam25 , Pinar Bulut26 , Christina Hajinicolaou27 , Victorien M. Wolters28 , Zerrin Önal29, Emmanuel M. Gonzales30 , Emmanuel Jacquemin30 , Jérôme Bouligand31 , Lorenzo D'Antiga32 , Emanuele Nicastro32 , Noelle H. Ebel33 , Jeffrey A. Feinstein34 , Björn Fischler35 , Henrik Arnell36 , Susan Siew37 , Michael Stormon37 , Kyung Mo Kim38 , Seak Hee Oh38 , Amin J. Roberts39, Helen M. Evans39, Maria Camila Sanchez40 , Maria Lorena Cavalieri40 , Way Seah Lee41 , Chatmanee Lertudomphonwanit42 , Ryan T. Fischer43 , Orith Waisbourd-Zinman44 , James E. Squires45 , Cigdem Arikan46 , Jesus Quintero Bernabeu47,48 , Mureo Kasahara49, Elisa Carvalho50 , Cristina Targa Ferreira51 , Pamela L. Valentino52 , Giuseppe Indolfi53 , John Eshun54 , Pier Luigi Calvo55 , Dev M. Desai56 , Aglaia Zellos57 , Antal Dezsőfi58 , Sabina Wiecek59, Gabriella Nebbia60 , Raquel Borges Pinto61 , Maria Rogalidou62 , María Legarda Tamara63 , Andréanne N. Zizzo64 , Jennifer Garcia65 , Kathleen Schwarz66 , Niviann Blondet52 , Marisa Beretta67 , Thomas Damgaard Sandahl68 , Jernej Brecelj69, Cristina Gonçalves70,71 , Eberhard Lurz72 , Ermelinda SantosSilva73 , Nanda Kerkar74 , Quais Mujawar75 , Christos Tzivinikos76 , Carolina Jimenez-Rivera77 , Jesus M. Banales78 , Richard J. Thompson79, Bettina E. Hansen80, 81 , Binita M. Kamath1 , and The Global ALagille Alliance (GALA) Study Group

Development of Disease-Specific Growth Charts for Children with Alagille Syndrome: Results from The Gala Study Group

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PROOF FOR PRESERVED PRIMARY HEMOSTASIS IN PEDIATRIC CIRRHOTIC PATIENTS: RESULTS FROM HIGH THROUGHPUT STATIC AND DYNAMIC PLATELET ASSAYS

PROOF FOR PRESERVED PRIMARY HEMOSTASIS IN PEDIATRIC CIRRHOTIC PATIENTS: RESULTS FROM HIGH THROUGHPUT STATIC AND DYNAMIC PLATELET ASSAY

EFFICACY AND SAFETY OF ODEVIXIBAT OVER 48 WEEKS: POOLED DATA FROM THE PHASE 3 ASSERT AND ASSERT-EXT STUDIES IN PATIENTS WITH ALAGILLE SYNDROME

ABSTRACT: Objectives and Study: Cholestasis in Alagille syndrome (ALGS) is associated with bile acid (BA) accumulation in the liver with spill-over into the systemic circulation, as well as severe pruritus that can impair sleep. Here, we describe outcomes with odevixibat, an ileal BA transporter inhibitor, using pooled data from the phase 3 ASSERT and ASSERT-EXT trials in patients with ALGS. Methods: In ASSERT (NCT04674761), patients with ALGS with history of significant pruritus and elevated serum BAs (sBAs) were randomised 2:1 to odevixibat 120 µg/kg/day or placebo, respectively, for 24 weeks. Patients who completed ASSERT could enter ASSERT-EXT (NCT05035030), an ongoing, 72-week extension study where all patients received odevixibat 120 µg/kg/day. Here, data from odevixibat-treated patients in ASSERT and/or ASSERT-EXT were pooled (from first odevixibat dose to a data cut-off of 17 July 2023). Observer-reported scratching scores, sleep parameters, and sBA levels were assessed through 48 weeks of treatment. Results: At the data cut-off, the pooled population comprised 52 odevixibat-treated patients (mean age, 6.5 years; 48% female; median [range] odevixibat exposure, 73 [16–110] weeks). Odevixibat treatment for up to 48 weeks resulted in rapid and significant mean improvements in pruritus and reductions in sBA levels vs baseline (Figure). There were also significant decreases from baseline to weeks 45−48 in multiple sleep parameters, including tiredness and mean percentage of days patients needed help falling asleep, needed soothing, and slept with their caregiver (Figure). Treatment-emergent adverse events (TEAEs) were reported in 49 of 52 (94%) odevixibat-treated patients. The most common TEAE was diarrhoea (n=18/52 [35%]). At the data cut-off, 1 patient had a TEAE (blood bilirubin increased) that led to study discontinuation. Conclusions: In patients with ALGS, odevixibat treatment for up to 48 weeks led to significant improvements in pruritus and sleep and significant reductions in sBA levels. TEAEs in this pooled analysis were consistent with previously reported results