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IVIG failed to improve survival with native liver in infants with biliary atresia

BOSTON — Three infusions of intravenous immunoglobulin did not improve survival with native liver compared with controls in a cohort of infants with biliary atresia, according to data from a Late Breaker presented at The Liver Meeting 2016.

“Although treatment was feasible, acceptable and safe following hepatoportoenterostomy in infants with biliary atresia, [intravenous immunoglobulin] should not be pursued further as a treatment for these patients,” Ronald J. Sokol, MD, of the section of pediatric gastroenterology, hepatology and nutrition in the department of pediatrics at the University of Colorado School of Medicine, said during his presentation.

Sokol suggested that a growing body of evidence indicates that inflammation or autoimmunity may contribute to the pathogenesis of biliary atresia. Because intravenous immunoglobulin (IVIG) has broad anti-inflammatory effects, the researchers conducted a phase 1/2a, open-label, clinical trial to determine whether this approach is feasible, acceptable, safe and effective in a cohort of 30 infants with biliary atresia who had undergone hepatic portoenterostomy.

The researchers assessed feasibility by evaluating the proportion of patients who received 80% or more of the three IVIG doses, acceptability as the ratio of families that allowed critical study procedures and safety as the ratio of serious adverse events, expected adverse events and toxicity. The efficacy outcome was good bile drainage, defined as the ratio of patients alive with native liver and serum total bilirubin less than 1.5 mg/dL at 90, 180 and 360 days after hepatic portoenterostomy, and survival with native liver at the 360-day point. Outcomes were compared with 64 historical controls. Patients did not receive corticosteroid treatment.

Of the 30 infants enrolled and 29 who met eligibility criteria, 97% completed the study. The feasibility and acceptability rate of the IVIG infusions was 79%. There were no serious adverse events reported that were associated with the treatment. The adverse event rate was 28%, which was expected, according to Sokol.

Baseline characteristics of study patients and controls were comparable. Good bile drainage was reported in 38% of the study group and 47% of controls at 90 days (P > .05). At 180 days, the rates were 48% for study patients and 52% for controls, while the good bile drainage rates were 24% for study patients and 44% for controls at 360 days (P > .05 for both).

Survival with native liver at 360 days occurred in 59% of the IVIG group and 71% of controls (P > .05).

“In this phase 1/2A study, three infusions of IVIG were administered without difficulty or safety concerns and were acceptable to caregivers,” the researchers concluded. “Compared to the historical control group, IVIG therapy following [hepatic portoenterostomy] for [biliary atresia] did not result in significantly improved bile drainage at 90, 180 or 360 days post-[hepatic portoenterostomy] or greater [survival with native liver] at 360 days.”- by Rob Volansky

Reference:

Sokol RJ, et al. Abstract LB-8. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.

Disclosures: Sokol reports being on the advisory committees or review panels of Yahoo Health; consulting for Alnylam, Alexion, Ikaria, Otsuka American Pharmaceuticals, Retrophin and Roche; and receiving grant or research support from FFF Enterprises, Mead Johnson Nutritionals and Shire/Lumena.