Bloodstream infection associated with biologic and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a nationwide registry-based case-control study 2010–2024

Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) improve outcomes in rheumatoid arthritis (RA), but concerns remain regarding serious infections, including bloodstream infections (BSI). We investigated the risk of first-time BSI associated with tumour necrosis factor-α inhibitors (TNFi), abatacept, interleukin-6 receptor inhibitors (IL-6Ri), and Janus kinase inhibitors (JAKi) in individuals with RA. Nationwide nested case-control study in Denmark including individuals with RA and first-time microbiologically confirmed BSI between 2010 and 2024. Each case was matched with five controls on birth year and sex using risk-set sampling. Associations between b/tsDMARD exposure and BSI were estimated using conditional logistic regression. Analyses stratified by individual drug, concomitant immunosuppressive therapy, and BSI pathogen were performed. We included 4,128 cases and 20,582 controls. Use of TNFi (adjusted incidence rate ratio (aIRR) 1.23, 95% CI 1.10–1.38) and IL-6Ri (aIRR 1.38, 95% CI 1.09–1.76) was associated with higher rates of BSI compared with no b/tsDMARD use, whereas abatacept (aIRR 0.71, 95% CI 0.47–1.07) and JAKi (aIRR 0.97, 95% CI 0.64–1.48) were not. Within the TNFi class, the signal was primarily driven by golimumab (aIRR 2.40, 95% CI 1.45–3.99) and infliximab (aIRR 1.47, 95% CI 1.17–1.85). Within IL-6Ri, the association was driven by tocilizumab (aIRR 1.42, 95% CI 1.10–1.83). In head-to-head comparisons, IL-6Ri use was associated with higher BSI rates than TNFi (aIRR 1.42, 95% CI 1.01–1.99). Concomitant glucocorticoid use was associated with increased BSI rates among TNFi and IL-6Ri users compared to monotherapy, whereas estimates among abatacept and JAKi users were imprecise. In pathogen-specific analyses, TNFi use was associated with higher rates of Staphylococcus aureus BSI (aIRR 1.68, 95% CI 1.27–2.22) and JAKi use with K. pneumoniae BSI (aIRR 5.48, 95% CI 1.34–22.35). TNFi and IL-6Ri use were associated with higher BSI rates in individuals with RA, whereas no overall associations were observed for abatacept or JAKi. BSI rates varied across individual agents and pathogens, and concomitant glucocorticoid use was associated with higher BSI rates among TNFi and IL-6Ri users.