Letter: Double‐Dose Hepatitis B Vaccination in IBD —A Step Forward in Protecting Immunosuppressed Patients. Authors' Reply

We thank the authors for their thoughtful and constructive comments on our study evaluating double-dose versus standard-dose hepatitis B virus vaccination in patients with inflammatory bowel disease [1, 2]. We appreciate their recognition of the clinical relevance of optimising vaccination strategies in regions where HBV prevalence remains substantial and immunosuppressive therapy is widely used. We are encouraged that the potential practical implications of our study have been highlighted, particularly the improved immunogenicity achieved with a simple dose modification using readily available vaccines. As noted, this approach may be especially valuable in settings where access to newer adjuvanted formulations is limited and where prevention of HBV infection is a critical component of IBD care. We agree that several important questions remain. Our study primarily evaluated short-term immunogenicity, and the durability of vaccine-induced protection following a double-dose regimen requires further longitudinal assessment. However, declining antibody titres represent a time-dependent physiological feature of normal immune kinetics, as demonstrated in several studies [3, 4]. Ulrich et al. reported a progressive decline in protective anti-HBs titres over time in both patients with IBD and healthy controls, without any occurrence of new HBV infection during a median follow up of 9.4 years [4]. Similarly, Yuen et al. observed no cases of chronic HBV infection over 18 years of follow-up, despite many individuals having antibody titres below the conventional protective threshold [5]. Notably, transient increases in antibody levels at different time points have been attributed to anamnestic immune responses, which restore antibody titres following antigen exposure [5]. These observations raise important questions regarding the appropriateness of fixed serological thresholds for defining true protective immunity during long-term follow-up. We also acknowledge the need for validation in more diverse IBD populations. Although our cohort reflects real-world clinical practice and included a substantial proportion of patients receiving immunosuppressive therapy. The predominance of ulcerative colitis and the relatively limited number of patients treated with biologic agents, partly reflecting regional treatment patterns [6], may limit generalisability. Larger, multicentre studies including both ulcerative colitis and Crohn's disease are needed to confirm the consistency of these findings across broader IBD populations. In addition, given the expanding therapeutic landscape, further studies incorporating patients receiving newer biologic and non-biologic advanced therapies will be important to better define vaccine responses across different treatment exposures. Comparative effectiveness studies evaluating double-dose conventional vaccines against adjuvanted formulations, as well as structured revaccination protocols for primary non-responders, represent important future research priorities. Such studies would help refine individualised vaccination strategies based on treatment exposure and baseline risk. However, until a definitive optimal strategy is established, a simple dose escalation of the conventional hepatitis B vaccine appears to be a practical and accessible preventive approach in routine clinical practice. Anupam Kumar Singh: writing – original draft, writing – review and editing. Chhagan Lal Birda: writing – review and editing, writing – original draft. Usha Dutta: writing – review and editing. The authors' declarations of personal and financial interests are unchanged from those in the original article [2]. This article is linked to Singh et al. papers. To view these article, visit https://doi.org/10.1111/apt.70470 and https://doi.org/10.1111/apt.70581. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.