Reduction in Spontaneous Reporting Rates of Hemolysis with IVIG After Implementation of an Immunoaffinity Chromatography Step for Isoagglutinin Reduction

Isoagglutinins can mediate hemolytic reactions in non-O blood group patients receiving intravenous immunoglobulin G therapy (IVIG). An immunoaffinity chromatography (IAC) step recently introduced in the production process of IVIG (Privigen®, CSL Behring, King of Prussia, USA) effectively reduces isoagglutinins. We assessed the impact of the IAC step (Ig IsoLo®) on spontaneous hemolysis reporting rates for patients receiving Privigen® at baseline (no isoagglutinin reducing measures) and after IAC implementation. Hemolysis reporting rates for baseline (2008−2013) and after IAC implementation (2016−2017) were extracted from the CSL Global Safety Database using the Standard MedDRA Query “Hemolytic Disorders Broad”. In 2016−2017, the worldwide reporting rate of hemolysis decreased from 4.05 at baseline to 0.70 cases/1000 kg Privigen® (83% reduction); cases of patients reported requiring blood/RBC transfusion decreased from 0.97 to 0.19 cases/1000 kg (80% reduction). In 2017 alone, when the proportion of IAC lots on the market was higher than in 2016, the hemolysis reporting rate was 0.32 cases/1000 kg (92% reduction) and only 1 patient required transfusion. Most patients experiencing hemolysis received IVIG for immunomodulatory therapy; hemolysis rate in these patients decreased from 3.09 to 0.52 cases/1000 kg. In patients on replacement therapy, hemolysis rate decreased from 0.28 to 0.12 cases/1000 kg. Reduction in hemolysis rate was greatest in patients with blood groups A and AB who are known to be at high risk. Introduction of IAC isoagglutinin reduction step in the manufacturing process of an IVIG substantially reduced hemolysis reporting rates and the requirement for blood/RBC transfusion.