Individualizing the dose of intravenous immune serum globulin for therapy of patients with primary humoral immunodeficiency

Abstract

The availability of safe and effective IgG preparations for replacement therapy for patients with primary disorders of humoral immunity allows almost unlimited doses of IgG to be used. Thus, knowledge of the optimal dose and serum concentration of IgG to be achieved is of practical importance. In a multicenter study of a reduced and alkylated IgG preparation (MISG), it was shown that the MISG was well tolerated and as effective as the intramuscular immune serum globulin (ISG) used for more than 30 years. During the course of this study, we observed that the standard dose of 100 mg/kg/month resulted in a wide range of IgG levels. We began a study using another intravenous IgG preparation to determine whether the variable IgG levels were due to variability in the half-life of IgG in these patients and whether an individualized dose of IgG could be calculated based on the half-life for each patient. The half-life was greatly prolonged, ranging from 26 to 86 days compared with 21 days in normal individuals. However, there was no correlation between the half-life and the serum IgG concentration over the range of concentrations measured. When patients were treated with higher doses of IgG, based on the amount calculated to raise the serum IgG concentration to 200 mg/dl, only 1 patient actually achieved that level and only 3 had a significant increase in the serum concentration despite the higher dose. Failure to achieve the predicted levels could not be explained by a shortened half-life and seemed to be related to increased losses in the early, redistribution, phase. The half-life was not reduced in patients who did achieve higher serum IgG concentrations, suggesting that the half-life is characteristic for each patient and not directly dependent on the serum IgG concentration. However, only modest increases were observed and additional studies using much higher doses of IgG will be necessary before this issue can be settled. Similarly, we did not see an additional benefit in those patients receiving higher doses of IgG, and further studies will be necessary before it can be determined whether higher levels of IgG can reduce the incidence of chronic infections and justify the increased time and expense. The results of the completed study have been published elsewhere [7].