Risk factors forStaphylococcus aureusbacteremia in patients with rheumatoid arthritis and incidence compared with the general population: protocol for a Danish nationwide observational cohort study

Abstract

IntroductionStaphylococcus aureusbacteremia (SAB) is an invasive infection with high mortality and morbidity. Rheumatoid arthritis (RA) is associated with increased risk of infections due to the disease per se and the use of antirheumatic treatments. Few minor studies have previously investigated risk of SAB in patients with RA and indicated increased risk compared with the general population. This nationwide observational study aims to investigate incidence of and risk factors for SAB in adult patients with RA compared with the general population. The effect of disease characteristics (eg, joint erosions, disease duration and activity), different antirheumatic treatments and smoking on SAB risk will be evaluated.Methods and analysisAll adults (>18 years of age) alive and living in Denmark in 1996–2017 will be identified in The Danish Civil Registration System. Incident patients with RA are identified in the Danish National Patient Registry (DNPR) and the nationwide rheumatology registry, DANBIO, in which information on, for example, antirheumatic treatments, disease characteristics and smoking is collected prospectively in routine care. Information on comorbidities, invasive procedures and prescribed drugs are identified in the DNPR and in The Register of Medicinal Product Statistics. Socioeconomic status is evaluated in national registers on income and education. Incident cases of first-time SAB are identified in The Danish National SAB Database. All registers are linked on an individual level by unique civil registration numbers. Incidence rates and incidence rate ratios will be analysed using Poisson regression models and the impact of possible risk factors will be evaluated.Ethics and disseminationAll data will be handled in accordance with the General Data Protection Regulation (EU) 2016/679. No ethical approval is necessary in Denmark when handling registry data only. The results will be presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology initiative in international peer-reviewed journals and at medical conferences.Trial registration numberNCT03908086.

Antirheumatic treatment, disease activity and risk ofStaphylococcus aureusbacteraemia in rheumatoid arthritis: a nationwide nested case–control study

“…The exposures of main interest were predefined and included treatment with bDMARDs and glucocorticoids as well as RA disease activity. 24 Users of bDMARDs had received any bDMARD (according to DANBIO) 0-24 months prior to the index date, as opposed to non-users. We subcategorised users according to most recent bDMARD use into either current (0-3 months prior to the index date, 0-12 months for rituximab) or former users (>3 months prior to index date, >12 months for rituximab).…”

At Early Rheumatoid Arthritis Stage, the Infectious Spectrum Is Driven by Non-Familial Factors and Anti-CCP Immunization

“…The special relationships of the immune system with St. aureus were confirmed by a number of authors. Dieperink et al demonstrated the increased risk of infection due to the RA disease per se regardless of the therapy [61]. The staphylococcal superantigen D gene was found in the synovial fluid and blood of RA patients [62].…”

Editorial: The interplay between the oral Microbiota and rheumatoid arthritis

“…Beyond articular damage, established RA also substantially increases the risk of systemic complications, such as lymphomas, myocardial infarctions, interstitial fibrosis or susceptibility to infections. Specifically, recent evidence indicates that RA patients display and increased risk of Staphylococcus aureus bacteraemia ( 23 , 24 ). This increased risk may be partially explained by an imbalance in inflammatory pathways during RA pathogenesis, and the use of antirheumatic treatments, that together impair immunity.…”