Analysis of trough levels of total IgG, IgG subclasses, measles neutralizing antibodies and IgG antibodies to encapsulated pathogens after infusion of a 5% or 10% intravenous immunoglobulin

Abstract

IntroductionPatients with primary immunodeficiency (PI) are at risk of infection due to low IgG levels. We report trough levels of total IgG, IgG subclasses, measles neutralizing antibody (MVab) titers, Haemophilus influenzae type B and seven Streptococcus pneumoniae serotypes in PI patients receiving a 5% and 10% intravenous immunoglobulin (IVIG) formulation. MethodsGMX07 was a bioequivalence trial comparing Gammaplex 10% IVIG with Gammaplex 5% IVIG in patients with PI. Adult patients received the 5% for ≥ five infusions, then the 10% for ≥ five infusions, or vice versa. Pediatric patients received the 10% for 5 infusions. Doses were 300–800 mg/kg/infusion. Trough IgG levels were measured before each infusion. Trough levels for MVab, H. influenzae and S. pneumoniae titers were measured after the last infusion. Results33 adults received the 5%, 32 received the 10%. 15 pediatric patients received the 10%. In adults, median IgG trough levels = 952.5 mg/dL for the 10% and 937.0 mg/dL for the 5%. In pediatric patients, median trough level = 879.5 mg/dL. Trough levels of IgG subclasses were comparable across formulations and age groups. Adult patients had a mean MVab titer of 2908 mIU/mL with the 5% vs 3213 mIU/mL for the 10%. In pediatric patients, mean MVab titer was 2122 mIU/mL. In adults, median trough levels of IgG antibodies to H. influenzae were 2.80 µg/mL for the 5% and 2.76 µg/mL for the 10%. Trough levels of IgG antibodies to all S. pneumoniae serotypes were consistent across formulations and age groups. No clinically meaningful differences were noted between formulations, 21-day vs 28-day regimens, or age groups. DiscussionMaintaining IgG trough levels and mean MVab trough titers above protective thresholds is critical for patients with PI. No trough levels or titers fell below the protective thresholds. While thresholds for protective levels for H. influenzae or S. pneumoniae are not clearly defined, delivery of these antibodies to PI patients was demonstrated. ConclusionOur results indicate protective trough levels of IgG and antibody titers are delivered with the 5% and 10% formulations of this IVIG product, with similar results for adult and pediatric PI patients.