Background/Purpose: Subjects with rheumatoid arthritis (RA) are at increased risk of cardiovascular (CV) morbidity and mortality, with some studies suggesting an increased risk of stroke (CVA). The aim of the analysis was to study the association of anti-TNF therapy with ischemic CVA (isCVA) in routine clinical practice.

Methods: The BSRBR-RA is an ongoing national prospective cohort study of subjects with RA recently started on anti-TNF therapy (etanercept, infliximab, adalimumab). A biologic-naïve comparator cohort of subjects with RA treated only with non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) was also recruited. Both cohorts were recruited from 2001-2008 and were followed by physician and patient questionnaires every six months for the first three years and annual physician questionnaires thereafter, in which data on serious adverse events such as CVAs and drug therapy were reported. All subjects were also linked to the national death register. Further data about reported CVAs were collected from medical records and validated against the World Health Organization criteria for CVA. These were further classified as isCVA using CT brain reports or if isCVA was reported as the underlying cause of death from death certificates using International Classification of Diseases 10 (ICD-10) code I63. Only validated isCVAs were included in the analysis. Subjects with prior CVA were excluded. Subjects were censored at first isCVA, death or date of last physician follow-up, whichever came first. Risk of isCVA was compared between the nbDMARD cohort and subjects ever exposed to anti-TNF using a Cox regression model. Adjustment was made using propensity scores stratified by deciles, which included age, gender, ethnicity, BMI, DAS28, disease duration, HAQ, prior nbDMARD use, steroid use at baseline, year of entry to study, smoking, baseline drugs including NSAIDs, digoxin, warfarin, antiplatelet agents, statins, history of cancer, hypertension, ischaemic heart disease, diabetes, depression and chronic lung disease.  

Results: To 10/31/2010, 130 verified incident isCVA (21 in 3271 nbDMARD subjects, 109 in 11642 anti-TNF subjects) occurred during 11973 and 61226 person-years (pyrs) of observation respectively (incidence rate 175 versus 178 per 100,000 pyrs). After adjustment, there was no association between ever exposure to anti-TNF and isCVA risk: hazard ratio (HR) 0.88 (95% CI 0.46, 1.71).

Conclusion: Exposure to anti-TNF therapy does not appear to be associated with the risk of isCVA over the short term when compared to nbDMARD therapy. Further follow-up is needed to assess time-varying risk.

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