Hepatitis B Vaccination in IBD

February 10, 2026

Issue 03

Clinical Question

Does double-dose hepatitis B vaccination improve immunogenicity in patients with inflammatory bowel disease?

Editor’s Bottom Line

Responses to monovalent hepatitis B vaccines (HBV) are attenuated by tofacitinib and anti- tumour necrosis factor (TNF) therapy. Higher doses of vaccine improve efficacy in all inflammatory bowel disease (IBD) patients, including those on immunosuppression.

Reference

Singh AK, Soni RK, Jearth V, et al. Clinical Trial: Immunogenicity of Double-Dose Versus Standard-Dose of Hepatitis B Virus Vaccine in Inflammatory Bowel Disease. Aliment Pharmacol Ther. Epub ahead of print Nov 20, 2025. https://doi.org/10.1111/apt.70470

Synopsis

This was a single-center, phase 3, randomized, double-blind trial conducted at a tertiary medical center in Chandigarh, India, between July 2022 and March 2024. Eighty-eight patients with IBD were randomized to receive either standard-dose (20μg) or double-dose (40μg) HBV (Engerix-B) at 0, 1, and 6 months. Patients were 18 years of age or older with confirmed IBD, were seronegative for hepatitis B markers, had no prior HBV vaccination and had anti-HBs titers <10 IU/L. Anti-HBs titers were measured one month after the third dose.

The primary outcome was adequate immune response (AIR), defined as anti-HBs >10 IU/L. Secondary outcomes included effective immune response (EIR), defined as anti-HBs >100 IU/L, and seroconversion stratified by disease activity. Ninety percent of patients had ulcerative colitis, the mean age was 36 years, 53% were female and 56% had active disease. The standard-dose group had a higher proportion of males (64.4% vs. 41.9%, p=0.034). Overall, 72% of patients received immunosuppressive therapy during the study.

In an intention-to-treat analysis, AIR was significantly higher with double-dose vaccination (88.4% vs. 55.6%; p=0.001) as was EIR (69.8% vs. 46.7%; p=0.028). Per-protocol analysis showed similar results, with both AIR (92.7% vs. 56.8%; p<0.001) and EIR (73.2% vs. 47.7%; p=0.017) higher with a double-dose.

Among patients with active disease, double-dose vaccination achieved significantly higher AIR (87.5% vs. 44%; p=0.001) and EIR (70.8% vs. 32%; p=0.007). However, in patients in remission, differences were not statistically significant.

Among patients receiving immunosuppressive therapy (n=63), 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). However, among patients not on immunosuppressive therapy (n=25), seroconversion rates did not differ significantly between groups.

Patients on tofacitinib or anti-TNF therapy had significantly lower AIR and EIR rates compared to those without immunosuppression (p=0.011 and p=0.001 for AIR; p=0.031 and p=0.013 for EIR).

On multivariable logistic regression, independent predictors of AIR included double-dose vaccination (Odds Ratio [OR]: 11.63; 95% Confidence Interval, 2.63-51.46) and anti-TNF use (OR: 0.03; 95% CI, 0.002-0.6). For EIR, double-dose vaccination (OR: 3.52; 95% CI, 1.04-11.92), albumin levels (OR: 1.13; 95% CI, 1.02-1.25) and male gender (OR: 0.08; 95% CI, 0.02-0.35) were significant predictors.

Adverse events occurred in 5.7% of patients (4.4% with standard-dose vs. 7% with double-dose; p=0.607). All were grade 1 or 2 and were managed conservatively.

Details

Study Design: Phase 3 randomized, double-blind clinical trial
Funding: Not specified
Allocation: Randomized
Setting: Single-center
Level of Evidence: 1b