STAR SIGN study: Evaluation of COVID‐19 vaccine efficacy against the SARS‐CoV‐2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease.

Summary: Background: Vaccine‐elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated with anti‐TNF biologics. Aims: To assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 in immunosuppressed patients with IBD. Methods: This prospective multicentre case–control study included 98 biologic‐treated patients with IBD and 48 healthy controls. Anti‐spike IgG concentrations and surrogate neutralisation against SARS‐CoV‐2 wild‐type, BA.1, BA.5, BQ.1.1, and XBB.1.5 were measured at two different time points (2–16 weeks and 22–40 weeks) following third dose vaccination. Surrogate neutralisation was based on antibody‐mediated blockage of ACE2‐spike protein–protein interaction. Primary outcome was surrogate neutralisation against tested SARS‐CoV‐2 sublineages. Secondary outcomes were proportions of participants with insufficient surrogate neutralisation, impact of breakthrough infection, and correlation of surrogate neutralisation with anti‐spike IgG concentration. Results: Surrogate neutralisation against all tested sublineages was reduced in patients with IBD who were treated with anti‐TNF biologics compared to patients treated with non‐anti‐TNF biologics and healthy controls (each p ≤ 0.001) at visit 1. Anti‐TNF therapy (odds ratio 0.29 [95% CI 0.19–0.46]) and time since vaccination (0.85 [0.72–1.00]) were associated with low, and mRNA‐1273 vaccination (1.86 [1.12–3.08]) with high wild‐type surrogate neutralisation in a β‐regression model. Accordingly, higher proportions of patients treated with anti‐TNF biologics had insufficient surrogate neutralisation against omicron sublineages at visit 1 compared to patients treated with non‐anti‐TNF biologics and healthy controls (each p ≤ 0.015). Surrogate neutralisation against all tested sublineages decreased over time but was increased by breakthrough infection. Anti‐spike IgG concentrations correlated with surrogate neutralisation. Conclusions: Patients with IBD who are treated with anti‐TNF biologics show impaired neutralisation against novel omicron sublineages BQ.1.1 and XBB.1.5 and may benefit from prioritisation for future variant‐adapted vaccines. [ABSTRACT FROM AUTHOR]