Editorial: Shingles Risk in <scp>IBD</scp> —More Evidence to Support Routine Preventive Vaccination?

Herpes zoster (HZ) results from the reactivation of latent varicella-zoster virus leading to dermatomal rash and pain. Although usually mild, complications may range from post-herpetic neuralgia, sight-threatening ophthalmic involvement and (rarely) life-threatening disseminated zoster. In adults, HZ incidence is 3–5 per 1000 person-years (PY), rising steeply with age [1]. People with IBD face a 1.7-fold higher risk than the general population [2] with the suggestion that the risk increases with steroids, traditional immunosuppressants, some biological therapies and JAK inhibitors (JAKi). There have been multiple systematic reviews and meta-analyses of HZ risk among participants in placebo-controlled RCTs of advanced therapies (for immune-mediated diseases in general and IBD in particular) including attempts at indirect comparison between drug classes using network analysis [3]. Findings have varied but a signal for JAKi appears more consistent or stronger than for other classes. However, direct safety comparisons based on head-to-head RCTs are lacking. Trial populations differ from real-world cohorts and observational studies may provide further insight. Estimating relative risk (RR) of different agents is challenging given the complexities of measured and unmeasured confounding. Ahuja et al. explored RR of HZ for individual drug classes using propensity methods (US claims database) [4]. The authors considered multiple confounders including patient characteristics and time bias (calendar year of initiation). Their findings agree with signals from RCTs [3], and suggest a 1.7- to 2.2-fold higher RR of HZ with JAKi (incidence: 3.3 per 100 PY versus 1.0 to 1.4 per 100 PY for other classes) [4]. RR of complicated HZ was non-significantly increased (incidence: 9 vs. 3–5 per 1000 PY) but its rarity limited study power [4]. This study generated estimates of RRs for different drug classes but not between different JAKis. The population included patients exposed to tofacitinib or upadacitinib but not filgotinib, and no data were presented on relative numbers receiving each agent. In theory, the signal could be driven by one (rather than both) drug. The research focused on HZ events alone without exploring the burden of other adverse events, including serious infections. Demonstrating an absence of class effect for non-HZ-related infections would have been interesting, as would reporting RRs of drug persistence following HZ events. HZ risk is relevant for most IBD patients, since there may be inherent risk posed by the disease itself [2], and exposure to steroids, conventional immunosuppressants and some advanced therapies [5-8]. IBD services may wish to advocate early vaccination for all patients, although there is no robust evidence for the cost-effectiveness of pre-emptive protection. UK IBD guidelines suggest ‘Recombinant zoster vaccination (Shingrix) should be considered in all patients aged 50 or over receiving any immunomodulators or advanced therapies, and patients aged 18 and over starting JAK inhibitors. All adults aged 50 years and over (regardless of therapy) are now eligible for recombinant zoster vaccination’ [9]. From September 2025, official UK vaccination guidance recommends ‘eligible individuals anticipating immunosuppressive therapy should ideally be assessed for [Shingrix] vaccine eligibility before starting treatment’ [10]. Keith Bodger: writing – original draft. This article is linked to Ahuja et al. papers. To view this article, visit https://doi.org/10.1111/apt.70418. The author has nothing to report.