Association between ischaemic stroke and tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of ischaemic stroke (IS). Drugs inhibiting tumour necrosis factor alpha (TNFi) may influence the risk and mortality post-IS by reducing inflammation. The aim of this analysis was to study the association of TNFi with (1) the risk of incident IS and (2) 30-day and 1-year mortality post-IS. METHODS: Patients with RA commencing TNFi, and a biologic-naive comparator group treated only with synthetic disease modifying anti-rheumatic drugs (sDMARDs), were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) from 2001 to 2009. Patients were followed via clinical and patient questionnaires, as well as the national death register. Incident strokes were classified as IS if brain imaging reports suggested ischaemia or if IS was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of IS was compared between patients receiving sDMARDs only and those ever- exposed to TNFi using a Cox regression model, adjusted for potential confounders. Mortality post-IS was compared between sDMARD-treated patients and TNFi-treated patients using logistic regression, adjusted for age and gender. RESULTS: To April 2010, 127 verified incident IS (21 in 3271 sDMARD patients; 106 in 11642 TNFi patients) occurred during 11973 and 61226 person-years of observation respectively (incidence rate 175 vs. 173 per 100 000 person-years). After adjustment for confounders, there was no association between ever-exposure to TNFi and IS: hazard ratio 0.99 (95% CI 0.54, 1.81). Thirty-day and 1-year mortality post-IS was not associated with concurrent TNFi exposure: odds ratio 0.18 (95%CI 0.03, 1.21) and 0.60 (95% CI 0.16, 2.28) respectively. CONCLUSIONS: Exposure to TNFi does not appear to influence the occurrence of IS in the medium term in patients with RA. The impact on post-IS mortality remains inconclusive. This article is protected by copyright. All rights reserved.