To compare the efficacy of
immunoglobulin replacement
therapy given intravenously versus subcutaneously to prevent
infections in patients with
primary antibody deficiency syndromes, an international, multicenter, open label, crossover study was designed. Forty patients were randomized to receive either subcutaneous or
intravenous immunoglobulin replacement
therapy for 1 year. In the second year, patients were switched to the alternative treatment, enabling patients to act as their own controls. Equivalent doses were given by both routes. Ethical approval was obtained from the review boards of the hospitals in which the patients were seen and written consent obtained from each patient. Patients with a
primary antibody deficiency syndrome, either
common variable immunodeficiency or
IgG subclass deficiency or specific antibody deficiency, who required
immunoglobulin replacement
therapy were included in the study. Patients were excluded if they had significant
thrombocytopenia (defined as platelets less than 50 x 10(9)/liter), had high levels of
anti-IgA antibodies (defined as greater than 1:8192), or had severe adverse reactions to a blood product within the last 2 years. The primary end point was the number of
infections and their severity (moderate and major) during the two treatment periods. Secondary end points were adverse reactions, length of
infections, days lost from school or work due to
infections, and acceptability of treatment regimens to the patients. Based on the assumption that it was difficult to prove equivalence of
therapies statistically in crossover studies, an arbitrary number of 40 patients was selected on the basis that this might be achievable in 2 years. There are no significant differences in efficacy or adverse reaction rates between
immunoglobulin replacement
therapy given subcutaneously or intravenously.