Tumor Necrosis Factor-α Inhibitors, Immune-Mediated Inflammatory Diseases, and Bloodstream Infections: Results from a Nationwide Case-Control Study.

OBJECTIVES: Severe infection risk associated with tumor necrosis factor-α inhibitors (TNFi) remains a concern. We aimed to assess the association between TNFi and bloodstream infections (BSI) in a population-based setting. METHODS: Nationwide, registry-based case-control study including all adults from 2010 to 2024 with a first-time microbiologically confirmed BSI (cases) compared to age and sex-matched controls from the general population. Users were defined as individuals with TNFi exposure within six months prior to the date of BSI. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. We further assessed risk variation by type of TNFi, pathogen, and underlying disease. RESULTS: We included 174,137 cases and 1,741,294 controls. Users had significantly increased odds of BSI compared to non-users (aOR: 1.41, 95% CI: 1.30-1.52), driven by increased odds among users of adalimumab and infliximab (aOR: 1.51, 95% CI: 1.33-1.72, and aOR: 2.01, 95% CI: 1.76-2.29). Use of certolizumab pegol and etanercept was associated with lower odds of BSI, and golimumab with higher odds compared to non-use, although not statistically significant. Species-specific analyses showed increased odds of BSI with Escherichia coli (aOR: 1.33, 95% CI: 1.16-1.53), Staphylococcus aureus (aOR: 1.69, 95% CI: 1.40-2.06), Streptococcus pneumoniae (aOR: 1.46, 95% CI: 1.05-2.04), and Enterococcus faecium (aOR: 1.62, 95% CI: 1.04-2.53). Highest odds were observed in individuals with inflammatory bowel disease (aOR: 2.27, 95% CI: 1.93-2.66), followed by individuals with rheumatoid arthritis. Compared to TNFi monotherapy, concomitant glucocorticoids increased the odds (aOR: 2.63, 95% CI: 2.06-3.36). CONCLUSIONS: TNFi use is associated with increased odds of BSI and was observed across the most frequent species. Odds varied by TNFi type and underlying disease, with highest odds among patients with inflammatory bowel disease, emphasizing the need for individualized infection risk assessment.