We read with great interest the trial by Singh et al. comparing double-dose versus standard-dose hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) 1. This study from India is particularly timely: HBV prevalence remains high in low socio-demographic index countries where IBD incidence is rising 2. As immunosuppressive therapy can trigger HBV reactivation with potentially fatal consequences 3, optimising vaccination strategies is paramount. The findings are compelling: double-dose vaccination achieved significantly higher adequate immune response (88.4% vs. 55.6%) and effective immune response (69.8% vs. 46.7%) rates as compared to standard dose. By using an identical schedule for both arms, Singh et al. elegantly isolate the effect of antigen dose on immunogenicity, extending earlier observations 4. The benefit was most pronounced in patients on immunosuppressive therapy—precisely the population where anti-TNF agents and immunomodulators consistently attenuate vaccine responses 5, 6. These results carry important practical implications. Guidelines recommend HBV vaccination for all seronegative IBD patients, ideally before initiating immunosuppression 7. However, the standard regimen achieves seroprotection in only approximately 61% of IBD patients versus over 95% in healthy individuals 8. The double-dose strategy offers an accessible solution using widely available vaccines, particularly relevant where newer adjuvanted formulations may be unavailable. Several questions merit further investigation. The durability of enhanced responses remains unknown. Given the predominantly ulcerative colitis population and limited representation of patients on biologics, validation in broader IBD cohorts is warranted. Comparative trials with adjuvanted vaccines such as Heplisav-B 9 and studies addressing non-responders through revaccination strategies would help define optimal approaches for different patient subgroups 10. Singh et al. provide valuable evidence that a simple dose modification can meaningfully improve HBV vaccine immunogenicity in IBD. We should consider incorporating this approach into preventive care protocols, particularly for patients on or anticipating immunosuppressive therapy. Luisa Bertin: conceptualization, investigation, writing – original draft. Edoardo Vincenzo Savarino: conceptualization, investigation, writing – review and editing, project administration. The authors have nothing to report. Edoardo Vincenzo Savarino has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots and Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, DiademaFarmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco and Zeta Farmaceutici. Luisa Bertin has served as speaker for Edra SPA, Takeda. 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.70603. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Bertin et al. (Sat,) studied this question.