Intradermal versus intramuscular hepatitis b re-vaccination in non-responsive chronic dialysis patients: a prospective randomized study with cost-effectiveness evaluation.

BACKGROUND: It has been calculated that 30% of chronic uraemic patients fail to produce antibodies to HBsAg antigen after hepatitis B (HB) vaccination. Low-dose intradermal (i.d.) inoculations and supplementary intramuscular (i.m.) injections have been reported to improve the response rate in previous non-responder chronic uraemic patients, but no cost-effectiveness evaluations have been made about this issue.
METHODS: We re-vaccinated 50 chronic dialysis patients, who did not have any detectable anti-HBs antibody after a reinforced protocol of hepatitis B vaccine given by i.m. route, with hepatitis B recombinant DNA yeast vaccine (80 micrograms) by intradermal (25 patients) or intramuscular (25 patients) administration (randomly allocated). We used the same amount of HBsAg in order to exclude the confounding effect of the dose level administered on the immune response of uraemic patients. We studied, over a 20-month follow-up, the persistence of anti-HBs antibodies in our responder vaccinees. We made a comparison between the costs of our re-vaccination protocol and the other re-vaccination strategies that have been recently suggested.
RESULTS: One month after completion of re-vaccination protocol, seroconversion rates (100% vs 48%, P = 0.008) and proportion of patients who elicited protective anti-HBs titres (96% vs 40%, P = 0.0001) were significantly higher in i.d. compared to i.m. patients. The levels of anti-HBs expressed as geometric mean titres and 95% confidence intervals (GMT (95% CI)), were significantly increased in i.d. than in i.m. groups, 100 (44-187) vs 26 (14-52) mUI/ml (P = 0.018). At month 12, the seroconversion rates were 57 vs 14% in i.d. and i.m. groups respectively (P = 0.158); the seroprotection rate was higher in i.d. individuals in comparison with i.m. patients, 50 vs 0%, P = 0.072. At month 20, the seroconversion rates were 54 and 0% among i.d. and i.m. patients respectively (P = 0.055); the seroprotection rate was higher in i.d. than in i.m. group (30 vs 0%, P = 0.2). At month 20, the median anti-HBs titres in i.d. patients were 21 mUI/ml, and GMT (95% CI) were 20.9 (2-54) mUI/ml. No important general or local side-effects were observed. The cost of our schedule was $92 US whereas the costs of other re-vaccination protocols ranged between 138 and $807 US.
CONCLUSIONS: Our results show that the unresponsiveness to recombinant yeast-derived vaccine may be mostly reversed by repeated low-dose i.d. injections of the same agent. In spite of an equal amount of HBsAg received, i.d. hepatitis B re-vaccination shows higher immunogenicity compared to i.m. administration over a 20-month observation period. Cost-effectiveness analysis demonstrated that the intradermal administration of HB vaccine is the most clinically effective re-vaccination strategy; it is also the most unexpensive one. We strongly recommend low-dose intradermal inoculations in order to re-vaccinate chronic dialysis patients who fail to respond to hepatitis B vaccination.

RCT Entities:   Population Interventions Outcomes