The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial.

BACKGROUND: In patients with hypogammaglobulinemia, substitution with immunoglobulin is the treatment of choice to reduce both frequency and severity of bacterial infections. Even with treatment, however, infections still occur in these patients.

OBJECTIVE: To determine whether doubling the standard dose of intravenous immunoglobulin would affect the incidence and duration of infections.

DESIGN: Multicenter, double-blind, randomized, crossover study.

SETTING: 15 outpatient clinics in the Netherlands.

PATIENTS: 43 patients with primary hypogammaglobulinemia, 41 of whom completed the protocol.

INTERVENTION: Patients received standard-dose immunoglobulin therapy for 9 months, followed by a 3-month washout period, and high-dose intravenous immunoglobulin therapy for 9 months, or vice versa.

MEASUREMENTS: The primary outcome measures were total number and duration of infections. Other measures were periods of fever, hospital admissions, use of antibiotics, absence from school or work, and trough levels of serum immunoglobulin. Side effects from the study medication were also recorded.

RESULTS: Compared with the standard dose of intravenous immunoglobulin (adults, 300 mg/kg of body weight every 4 weeks; children, 400 mg/kg every 4 weeks), high-dose therapy (adults, 600 mg/kg every 4 weeks; children, 800 mg/kg every 4 weeks) significantly reduced the number (3.5 vs. 2.5 per patient; P = 0.004) and duration (median, 33 days vs. 21 days; P = 0.015) of infections. Trough levels of IgG increased significantly during high-dose therapy. The incidence and type of side effects did not differ significantly for the two dosages.

CONCLUSION: In patients with hypogammaglobulinemia, doubling the standard dose of intravenous immunoglobulin significantly reduced the number and duration of infections.