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

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 multi-center, prospective, open-labeled, phase I/IIA trial of IVIg was conducted, with 1 gm/kg/dose of IVIg infused at 3–5 days, 30 days 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 to a historical placebo-arm group, there was no significant increase in the proportion of IVIg participants with a serum total bilirubin  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. Address correspondence and reprint requests to Cara L. Mack, MD, Children's Hospital Colorado, 13123 E. 16th Ave., B290, Aurora, CO 80045 (e-mail: cara.mack@childrenscolorado.org). Received 5 August, 2018 Accepted 26 November, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Funding source: 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 AwardsUL1 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. Clinical Trial Registration: Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants with Biliary Atresia (PRIME); #NCT01854827; http://bit.ly/2S1Gwy7 Contributors Statement: Drs. Cara Mack, and Ronald Sokol conceptualized and designed the study, coordinated and supervised data collection, assisted in data analyses, drafted the initial manuscript and edited the final version. Drs. Jorge Bezerra and Estella Alonso coordinated and supervised data collection, assisted in data analyses, drafted the initial manuscript and edited the final version. Cathie Spino and Jeffrey Moore carried performed all data analyses, provided biostatistical support and edited the final version. Drs. Vicky Ng, Saul Karpen, Venna Venkat, Kathleen Loomes, Kasper Wang and Catherine Goodhue coordinated and supervised data collection and edited the final version. Drs. Averell Sherker and John Magee assisted in the data analyses, provided important intellectual input and edited the final version. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Conflict of Interest and Source of Funding: The authors have no conflicts of interest or financial relationships with the sources of funding to disclose that are relevant to this article. No reprints requested. © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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