A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia

• Type of Material: Article
• Authors: Cara L. Mack, University of Colorado; Cathie Spino, University of Michigan, Ann Arbor; Estella M. Alonso, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL; Jorge A. Bezerra, Cincinnati Children's Hospital Medical Center; Jeffrey Moore, University of Michigan, Ann Arbor; Catherine Goodhue, Children's Hospital Los Angeles; Vicky L. Ng, University of Toronto; Saul Karpen, Emory University; Veena Venkat, University of Pittsburgh; Kathleen M. Loomes, The Children's Hospital of Philadelphia; Kasper Wang, Children's Hospital Los Angeles; Averell H. Sherker, National Institutes of Health (NIH); John C. Magee, University of Michigan, Ann Arbor; Ronald J. Sokol, University of Colorado
• Language: English
• Date: 2019-04-01
• Publisher: Wolters Kluwer
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/MPG.0000000000002256
• Title of Journal or Parent Work: Journal of Pediatric Gastroenterology and Nutrition
• Volume: 68
• Issue: 4
• Start Page: 495
• End Page: 501
• Grant/Funding Information: This work was supported by U01 grants from the National Institute of Diabetes, Digestive and Kidney Diseases (DK 62497 [to Dr. Bezerra], DK 62470 [to Dr. Karpen], DK 62481 [to Dr. Loomes], DK 62456 [to Ms. Spino], DK 62466 [to Dr. Venkat], DK 62453 [to Dr. Sokol], DK 84538 [to Dr. Wang], DK 62436 [to Dr. Alonso], and DK 642453 [to Dr. Ng]). In addition, the project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, UL1 TR001878 [The Children’s Hospital of Philadelphia], Clinical Translational Science Awards UL1 TR002535 [University of Colorado Denver] and the Cincinnati Center for Translational Science and Training [Cincinnati Children’s Hospital]. FFF Enterprises (Temecula, California) supplied and shipped the IVIg.
• Keywords: Male; Portoenterostomy, Hepatic; Biliary Atresia; Humans; Infant, Newborn; Prospective Studies; Liver Transplantation; Child, Preschool; Drainage; Immunoglobulins, Intravenous; Postoperative Complications; Treatment Outcome; Female; Infant
• Research Categories: Health Sciences, Nutrition; Health Sciences, General; Health Sciences, Pharmacy

Abstract

OBJECTIVES: Biliary atresia (BA) is a progressive neonatal fibroinflammatory cholangiopathy. We hypothesized that intravenous immunoglobulin (IVIg) would be safe, feasible, acceptable, and efficacious for the treatment of BA. The primary objective of this study was to establish the feasibility, acceptability, and safety profile of IVIg administration after hepatoportoenterostomy (HPE) in BA. The secondary objective was to determine the treatment efficacy of IVIg based on good bile drainage and survival with the native liver. METHODS: A multicenter, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 g/kg/dose of IVIg infused at 3-5, 30, and 60 days post-HPE, and subjects followed for 360 days post-HPE. Twenty-nine participants completed the study. RESULTS: Administration of IVIg infusions was feasible and acceptable in 79%. None of the serious adverse events (SAEs) were directly related to IVIg infusions; however, 90% of participants had an SAE. Compared with a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin <1.5 mg/dL at 90, 180, or 360 days post-HPE. Survival with the native liver in the IVIg participants showed no significant benefit over the historical placebo arm, with a difference at 360 days of -11.9% (IVIg: 58.6%, placebo: 70.5%; 90% UCB: 2.1%; P > 0.05). CONCLUSIONS: Although IVIg infusions in infants with BA post-HPE were feasible, acceptable and safe, there was no trend to lower bilirubin levels or improved 360-day survival with the native liver. CLINICAL TRIAL: Safety Study of Intravenous Immunoglobulin Post-Portoenterostomy in Biliary Atresia; #NCT01854827.