Pathogen‐Specific Bloodstream Infections Associated With Tumour Necrosis Factor‐α Inhibitors, Vedolizumab and Ustekinumab in Inflammatory Bowel Disease: A Danish Nationwide Case‐Control Study 2010–2024

ABSTRACT Background Biologic drugs have substantially expanded treatment options for inflammatory bowel disease (IBD), but infection risk during exposure remains a concern. Aims To investigate the association between current use of tumour necrosis factor‐α inhibitors (TNFi), vedolizumab and ustekinumab and bloodstream infection (BSI) in individuals with IBD. Methods Nationwide, registry‐based case‐control study including all individuals with a first‐time microbiologically confirmed BSI from 2010 to 2024 and an IBD diagnosis (cases). Each case was matched with five controls with IBD using risk‐set sampling. Current biologic use was defined as recorded use of either TNFi, vedolizumab or ustekinumab within 180 days before the index date. Adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results We included 4503 cases and 22,473 controls. TNFi use was associated with higher BSI rates compared with no current biologic use (aIRR 1.73, 95% CI 1.49–2.00), whereas vedolizumab (aIRR 0.85, 95% CI 0.61–1.20) and ustekinumab (aIRR 0.68, 95% CI 0.38–1.23) use was not. In pathogen‐specific analyses, TNFi use was associated with higher rates of BSI caused by Escherichia coli and Staphylococcus aureus , while vedolizumab use was associated with higher rates of Enterococcus faecium BSI. Concomitant glucocorticoid use was associated with increased BSI rates among TNFi and vedolizumab users compared with monotherapy. Conclusions TNFi use was associated with increased BSI rates in patients with IBD, whereas vedolizumab and ustekinumab use was not. Overall, the findings suggest potential differences in infection risk across biologic therapies and in pathogen‐specific susceptibility.