Aseptic meningitis following therapy with immune globulins: a combination of product features and patient characteristics?

BACKGROUND: Aseptic meningitis (AM) represents a recognized side effect of immune globulin (IG) therapy and may warrant additional diagnostic procedures and therapy with anti-infective drugs until a definite diagnosis can be established. Although, to date, only small case series have been published, the objective of the current study was to investigate a large case series of patients with AM. STUDY DESIGN AND METHODS: The pharmacovigilance safety database of a 10% liquid IG (Gammagard Liquid) was queried for all reports of AM. Patient demographics, treatment-specific data, and product-specific data were determined. The proportional reporting rates of AM were compared according to the route of administration (intravenous vs. subcutaneous) and molecular size distribution of IG lot (dimer content ≥ 8 vs. < 8%). RESULTS: In total, 144 AM episodes were reported in 136 distinct patients. Females were affected by AM nearly four times more than males. AM was not limited to patients who received high-dose IG therapies but was observed in those who received low-dose regimens in percentages comparable to the estimated usage patterns of IG. Lots that had high dimer values were associated with AM significantly more often than lots that had low dimer values (p < 0.001), and subcutaneous IG administration was associated with lower rates of AM compared with intravenous IG administration (p = 0.055). CONCLUSION: In contrast to previously published data, AM was observed in both low-dose and high-dose regimens without favoring high IG doses, and females were affected nearly four times more often than males. Immunoglobulin G dimers may play a role in the etiology of AM, and subcutaneous administration may be associated with a lower rate of AM compared with intravenous administration.

Hemolytic events after the administration of lyophilized versus liquid immune globulin: an analysis of a single manufacturer's safety database.

BACKGROUND: Recent publications have raised concerns that liquid immune globulins (IGs) may be associated with either a higher or a lower frequency of hemolytic events compared to lyophilized IGs, among other reasons due to the differences of their isohemagglutinin content. The aim of this study was to evaluate the relationship of hemolytic events to product presentation (liquid versus lyophilized) and to examine the relationship between total IG doses administered and the individual isohemagglutinin titers of IG lots infused. STUDY DESIGN AND METHODS: The reporting rate as well as the proportional reporting rate (PRR) of hemolytic events for liquid (Gammagard liquid [GGL]) and lyophilized IG (Gammagard S/D [GGSD]) received spontaneously from the United States was calculated. For all hemolytic events received spontaneously from global sources, total IG doses (g/kg body weight) and the loading dose of isohemagglutinins (total IG dose infused × isohemagglutinin titers of infused lots) were determined. RESULTS: With 0.27 and 0.33 cases per 1 million grams distributed, the reporting rates for GGL and GGSD are comparable, further confirmed by a PRR of 1.0 (95% confidence interval, 0.4-2.7). Hemolytic events for GGL and GGSD were observed with low loading doses of isohemagglutinins, and lots with high isohemagglutinin titers did not contribute to the development of hemolytic events in a higher proportion than lots with low titers CONCLUSIONS: Hemolysis associated with GGL or GGSD can occur even with low loading doses of isohemagglutinins. Data presented do not indicate that high isohemagglutinin titers of IG products play a major role in the development of these events.