We sincerely thank Hegde et al. for their thoughtful interest in our study and for their valuable comments on strategies to optimise hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) 1, 2. We appreciate their emphasis on the emerging role of adjuvanted HBV vaccines, particularly HepB-CpG (Hepatitis B vaccine with a cytosine phosphoguanine adjuvant), in this high-risk population. Our study showed that a double-dose regimen of Engerix-B (40 μg at 0, 1 and 6 months) significantly improved both adequate (88.4% vs. 55.6%) and effective (69.8% vs. 46.7%) immune response rates compared with the standard-dose regimen (20 μg at 0, 1 and 6 months) in patients with IBD 2. We agree that dose escalation alone may not fully overcome vaccine hyporesponsiveness in all patients, and limitations such as persistent non-response, adherence challenges and higher cost remain relevant. In this context, adjuvanted vaccines such as HepB-CpG represent a promising alternative 3. However, evidence regarding HepB-CpG in IBD remains limited and is still evolving. Kwon et al. were the first to retrospectively evaluate HepB-CpG in 106 patients with IBD who failed to achieve seroconversion after a standard HBV vaccination schedule, reporting an overall seroconversion rate (anti-HBs > 10 IU/L) of 78.3% after one or two doses 4. In a subsequent prospective study, Hegde et al. reported an overall seroconversion rate of 71.8% (61/85) 5. Among previously unvaccinated patients, seroconversion was achieved in 79% (50/63), whereas only 50% (11/22) of prior vaccine non-responders responded. Notably, among patients receiving systemic immunosuppression, the seroconversion rate was 63% (31/49). In our study, patients receiving immunosuppressive therapy achieved seroconversion in 87.5% (28/32) with the double-dose regimen, compared with 45.2% (14/31) with the standard-dose regimen 2. Although this appears numerically higher than that reported for HepB-CpG in immunosuppressed patients with IBD, direct comparisons should be interpreted cautiously because of differences in patient characteristics and immunosuppressive regimens. Head-to-head studies are needed before the superiority of one strategy can be established. Cost-effectiveness and availability are also important considerations. Prior analyses suggest that HepB-CpG may be more cost-effective than Engerix-B in immunosuppressed patients with IBD, whereas its benefit appears more modest in treatment-naive or previously unvaccinated patients 6. However, despite approval by the U.S. Food and Drug Administration (FDA) in 2017, HepB-CpG remains unavailable in most developing and underdeveloped countries, where the burden of hepatitis B virus infection is highest 7. In these settings, standard recombinant HBV vaccines continue to represent the only practical option. We also agree that prior vaccination history should be carefully considered when planning HBV immunisation. In previously vaccinated individuals with anti-HBs titers < 10 IU/L or incomplete vaccination history, a challenge dose may be a reasonable strategy to avoid unnecessary repeat full-series vaccination. Overall, the optimal HBV vaccination strategy in IBD should be individualised based on vaccine availability, prior vaccination history, immunosuppressive exposure and expected efficacy. Double-dose recombinant vaccination remains a practical and accessible strategy, while adjuvanted vaccines such as HepB-CpG may offer advantages where available. Further comparative studies are needed. Anupam Kumar Singh: conceptualization, writing – original draft, writing – review and editing, data curation. Chhagan Lal Birda: writing – review and editing. The authors' declarations of personal and financial interests are unchanged from those in the original article. The authors have nothing to report. This article is linked to Singh et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70470 and https://doi.org/10.1111/apt.70651. The authors have nothing to report.
Singh et al. (Wed,) studied this question.