Isoagglutinin reduction in intravenous immunoglobulin (IgPro10, Privigen) by specific immunoaffinity chromatography reduces its reporting rates of hemolytic reactions: an analysis of spontaneous adverse event reports

Abstract

BACKGROUND Hemolysis is an infrequent but recognized and potentially serious adverse effect of intravenous immunoglobulin (IVIG). Relatively elevated hemolysis reporting rates were seen with some IVIG products with high anti‐A/B isoagglutinin content, among which IgPro10 (Privigen, CSL Behring). For IgPro10, two isoagglutinin reduction measures were successively implemented: 1) anti‐A donor screening and 2) immunoaffinity chromatography (IAC; Ig IsoLo)–based isoagglutinin reduction step included in the production process. The aim of this analysis was to investigate the effects of these isoagglutinin reduction measures on the reporting rates of IgPro10 hemolysis worldwide. STUDY DESIGN AND METHODS Between February 2008 and December 2018, hemolysis reports from the CSL Behring Global Safety Database were analyzed in relationship to changes in IVIG IgPro10 production methods. Further analysis classified hemolysis reports by indication and blood group. RESULTS Median (minimum‐maximum) anti‐A/anti‐B titers were 32 (8‐64)/16 (8‐32) at baseline, 32 (8‐64)/16 (8‐32) after donor screening, and 8 (8‐32)/4 (2‐8) after implementation of IAC. The reporting rate of hemolytic reactions per 1000 kg IgPro10 sold was 4.05 cases at baseline, 2.00 after donor screening, and 0.50 after implementation of IAC. In 2018, there were seven reports of hemolytic reactions; representing 0.18 cases per 1000 kg IgPro10 sold, with a reduction of 95.6% versus baseline. CONCLUSION Following implementation of the IAC isoagglutinin reduction step, spontaneous reports of hemolytic events with IgPro10 were significantly and consistently reduced versus IgPro10 without isoagglutinin reduction, offering patients a more favorable benefit‐risk profile.

Incidence and risk factors for intravenous immunoglobulin‐related hemolysis: A systematic review of clinical trial and real‐world populations

“…Modern IVIG purification processes include anion exchange chromatography steps that increase the purity of IgG but do not reduce levels of isoagglutinins. Some IVIG purification processes include a specific immunoaffinity isoagglutinin reduction step, with a recent study showing that hemolytic events are significantly reduced from around 4.05 cases at baseline (per 1000 kg) to 0.50 cases when immunoaffinity chromatography (IAC) is utilized 46 . An overview of the main production processes and resulting isoagglutinin content is shown in Figure 2.…”

Intravenous Immunoglobulin-Associated Severe Hemolytic Anemia

“…The risk of hemolytic anemia is much higher with IVIG products, that have skipped the separation of FIII of the original ethanol fractionation process without another isoagglutinin reduction step [ 17 , 18 ]. IVIG products that have utilized further purification processes such as immunoaffinity chromatography (IAC) have demonstrated reduced rate of hemolysis [ 14 , 19 ].…”

Management of the sensitized pediatric renal transplant candidate

“…To address this, manufacturers have now included a column absorption step to remove anti‐A/B antibodies from the IVIg 22 . These products are referred to as “IsoLow.” This has significantly reduced the incidence of hemolysis after IVIg administration to blood group A, B, and AB individuals 23 …”

“…This has significantly reduced the incidence of hemolysis after IVIg administration to blood group A, B, and AB individuals. 23…”