Anti‐A/B isoagglutinin reduction in an intravenous immunoglobulin product and risk of hemolytic anemia: a hospital‐based cohort study

Abstract

BACKGROUND Intravenous immunoglobulins (IVIG) are derived from large human plasma pools. IVIG‐associated hemolytic anemia (HA) is a known class effect, likely attributed to dose‐dependent passive transfer of anti‐A/B isoagglutinins. Two isoagglutinin reduction steps were implemented in the manufacturing process of Privigen (human 10% liquid IVIG): exclusion of high–anti‐A–titer donors in 2013, replaced by specific immunoaffinity chromatography in 2015. We aim to estimate the clinical effectiveness of both measures. STUDY DESIGN AND METHODS Using the US hospital‐based Premier Healthcare Database, three Privigen cohorts were generated based on calendar periods indicative of manufacturing changes: Period 1 (baseline) January 2008 to December 2012, Period 2 (high–anti‐A–titer donor exclusion) October 2013 to December 2015, and Period 3 (immunoaffinity chromatography) October 2016 to April 2019. HA within a 10‐day at‐risk period after Privigen administrations was identified from review of patient record summaries. Incidence rate ratios (IRRs) were estimated from Poisson regression (Period 1 reference) adjusting for hospital setting, sex, age, Privigen indication, dose, and first use. RESULTS Crude incidence rates of HA were 1.49 per 10,000 person‐days in Period 1 (38 HA, 9439 patients), 1.01 in Period 2 (20 HA, 7710 patients), and 0.14 in Period 3 (3 HA, 7759 patients). Adjusted IRR for HA in Period 2 was 0.71 (95% confidence interval [CI], 0.41‐1.23), and in Period 3 was 0.10 (0.03‐0.33) compared with Period 1. The IRR for HA in Period 3 compared with Period 2 was 0.14 (95% CI, 0.04‐0.47). CONCLUSION Implementation of immunoaffinity chromatography in Privigen manufacturing resulted in a significant 90% reduction of HA risk. HA has become a rare event in association with Privigen use.