Clinical Trial: Immunogenicity of Double‐Dose Versus Standard‐Dose of Hepatitis B Virus Vaccine in Inflammatory Bowel Disease

BACKGROUND: Immunogenic response to hepatitis B virus (HBV) vaccine in patients with inflammatory bowel disease (IBD) is variable and often suboptimal. AIM: To compare the immunogenicity of standard-dose (20 μg) vs. double-dose (40 μg) HBV vaccination in patients with IBD. METHODS: We randomised patients with IBD 1:1 to receive standard- or double-dose HBV vaccine at 0, 1 and 6 months. Anti-HBs titres were measured 1 month after the third dose. The primary outcome was an adequate immune response (AIR; anti-HBs titre > 10 IU/L). Secondary outcomes included an effective immune response (EIR; anti-HBs titre > 100 IU/L) and seroconversion stratified by disease activity. RESULTS: We randomised 45 patients to the standard-dose and 43 to the double-dose. Overall, 63 patients (71.6%) achieved AIR, and 51 (57.9%) achieved EIR. Both AIR (88.4% vs. 55.6%, p = 0.001) and EIR (69.8% vs. 46.7%, p = 0.028) rates were significantly higher with the double-dose. Among patients receiving immunosuppressive therapy, double-dose vaccination demonstrated significantly higher AIR (87.5% vs. 45.2%, p < 0.001) and EIR (65.6% vs. 35.5%, p = 0.017), while differences were not significant in those without immunosuppression. On multivariable analysis, predictors of AIR included double-dose vaccination (odds ratio OR 11.63; 95% confidence interval CI 2.63-51.46) and anti-TNFs (OR 0.03; 95% CI 0.002-0.6). Double-dose vaccination was also associated with higher odds of achieving EIR (OR 3.52; 95% CI 1.04-11.92). CONCLUSIONS: Double-dose HBV vaccination significantly improved AIR and EIR over standard-dose. These findings support a double-dose strategy to optimize seroconversion in patients with IBD, especially those receiving immunosuppressive therapy.