RESUMO
BACKGROUND: End-stage renal disease and the need for chronic hemodialysis is an indication for hepatitis B vaccination, but up to half of dialysis patients fail to respond to a 40 microg/dose i.m. three-dose primary series of recombinant hepatitis B vaccine. Only another 10-20% respond to additional boosting doses of vaccine. PATIENTS AND METHODS: Since GM-CSF has been shown to be an effective adjuvant for hepatitis B vaccine in healthy subjects and multiple animal vaccine models, we conducted a randomized, double-blind trial of GM-CSF with recombinant hepatitis B vaccine in chronic hemodialysis patients. Patients with negative hepatitis B surface antibody and antigen who had received at least three doses of recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml) were randomized to placebo, 40 microg, or 80 microg of GM-CSF given with 40 microg recombinant hepatitis B vaccine i.m. at the same site. Clinical and laboratory studies for safety assessment were done on days 1 and 3, and hepatitis B surface antibody titres were measured at baseline and days 21 and 180 after the study injections. RESULTS: No significant local or systemic toxicity was noted from the co-injections. The rates of response and geometric mean titre (GMT) were equivalent among all three study groups: placebo 6/10 developed antibodies, GMT 22.1 mIU/ml; 40 microg GM-CSF 3/10 developed antibodies, GMT 5.4 mIU; and 80 microg GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after vaccination, antibody titres were available for 11 of the 12 day 21 positive responders; only 4 of these 11 patients remained antibody positive at 6 months. CONCLUSION: GM-CSF given in a single 40 microg and 80 microg i.m. dose was not an effective adjuvant with hepatitis B vaccine in chronic hemodialysis patients who had previously failed to respond to hepatitis B immunization.
