Long term use of intravenous immune globulin in patients with primary immunodeficiency diseases: Inadequacy of current dosage practices and approaches to the problem

Abstract

Thirty patients with well-defined primary immunodeficiency diseases seen at Duke University Medical Center between April of 1975 and November of 1981 were given modified immune serum globulin suitable for intravenous use (IGIV) for replacement therapy. Seven patients had infantile x-linked agammaglobulinemia (XAγ), three had x-linked immunodeficiency with hyper IgM (HypM), three had Wiskott-Aldrich syndrome, and 17 had common variable agammaglobulinemia (CVAγ). Twenty-two of the patients received a reduced and alkylated preparation (Gamimune®) over periods of up to five years and 21 have received a beta propriolactone-treated preparation (Intraglobulin®) over a period ranging to 7 months. Fourteen of the Gamimune-treated patients participated in the two-year crossover Phase II efficacy and safety study beginning in April of 1975 and 9 of these participated in the 6-month double-blind crossover study of 10% IGIV in glycine vs 5% IGIV in 10% maltose (Gamimune). Ten of the patients received Gamimune on a monthly basis for more than 5 years, with the other 12 receiving it for lesser periods of time. All patients received an initial loading dose of 200 mg/kg IgG and were maintained on 100 mg/kg/month thereafter. Adverse effects were most frequent with 10% IGIV in glycine and included primarily back and muscle pain, chills, nausea and vomiting; these have been rare with 5% IGIV in 10% maltose (Gamimune). No anaphylactic-type reactions occurred. No patient experienced adverse effects sufficiently severe to necessitate discontinuing a given infusion, and no patient dropped out of the study because of adverse effects. Patients participating in the two-year crossover study were given a choice as to the form of replacement therapy at the conclusion of the study: 10 elected to remain on Gamimune and the other four resumed plasma therapy; no patient elected to resume intramuscular ISG injections. Both intravenous preparations had excellent patient acceptability and have resulted in efficacy at least comparable to that of intramuscular ISG and plasma therapy. Patients with the Wiskott-Aldrich syndrome tolerated IGIV with no adverse effects and were cognizant of a reduction in their frequencies of pyogenic infections. A patient with persistent Echovirus meningoencephalitis was given 500 mg IgG/kg/month for 9 months but remained Echovirus positive.