Intradermal Versus Intramuscular Hepatitis B Vaccination in Hemodialysis Patients: A Prospective Open-Label Randomized Controlled Trial in Nonresponders to Primary Vaccination

Background: Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermai (ID) vaccination. Study Design: Prospective open-label randomized controlled trial. Setting & Participants: Hemodialysis patients nonresponsive to primary HBV vaccination. Intervention: Revaccination with either ID (5 mu g of vaccine every week for 8 weeks) or IM (40 mu g of vaccine at weeks 1 and 8) HBV vaccine. Outcomes: Primary outcome: proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. Secondary outcomes: time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. Measurements: Anti-HBs titer to 24 months. Results: 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% Cl, 131 to 434) versus 78 IU/L (95% Cl, 36 to 168; P < 0.001). There was a trend toward longer duration of seroprotection with ID vaccination. ID vaccine was safe and well tolerated. Limitations: Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. Conclusions: Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting. Am J Kidney Dis 54:95-103. 0 2009 by the National Kidney Foundation, Inc.