WASHINGTON – Exposure to anti-tumor necrosis factor therapy does not appear to be associated with a greater short-term risk of ischemic stroke in patients with rheumatoid arthritis when compared with exposure to nonbiologic disease-modifying antirheumatic drug therapy, according to findings from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.
Of 130 verified incident ischemic cerebrovascular accidents that occurred among participants in that large prospective cohort study of RA patients, 109 occurred in 11,642 patients treated with anti–tumor necrosis factor drugs (anti-TNFs) for an incidence rate of 178/100,000 person-years, and 21 occurred in 3,271 patients in a comparator group of biologic-naive patients who had been treated with only nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) for an incident rate of 175/100,000 person-years, Dr. Audrey S. Low reported at the annual meeting of the American College of Rheumatology.
The incident rates did not differ significantly, and no association was seen between ever exposure to anti-TNF drugs and ischemic stroke risk after adjustment for confounders using a propensity score based on age, sex, ethnicity, body mass index, disease activity score, disease duration, Health Assessment Questionnaire score, prior nbDMARD use, steroid use at baseline, year of entry to the study, smoking, baseline drugs, and history of cancer, hypertension, ischemic heart disease, diabetes, depression, and chronic lung disease (hazard ratio, 0.88), said Dr. Low of the University of Manchester (England).
Patients in the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) were recruited during 2001-2008 and were followed semiannually for 3 years, then annually thereafter. All serious adverse events, such as stroke, and all drug therapy were reported. Events reported through Oct. 21, 2010, were included in this analysis.
The investigators also linked study subjects to the national death register and collected information from medical records; a concerted effort was made to classify stroke types.
The anti-TNF and nbDMARD groups differed with respect to several factors: The anti-TNF cohort was younger, included more women, and had higher disease activity, longer disease duration, and higher levels of disability. That cohort also used more DMARDs, more steroids, and more nonsteroidal cyclo-oxygenase-2 (COX-2) inhibitors. However, the rates of hypertension and diabetes were similar in the anti-TNF and nbDMARD cohorts.
This study is among the largest to show that anti-TNF therapy does not increase stroke risk in RA patients, when compared with nbDMARDS, Dr. Low said.
"We know that patients with RA are at risk of increased cardiovascular morbidity and mortality, and that includes stroke," she said, noting that several other observational studies and meta-analyses have demonstrated an overall increase in that risk.
However, outcomes have varied in studies comparing anti-TNF–treated RA patients and controls, with some showing as much as a 60% increase in ischemic stroke risk and others demonstrating a 30% reduction in risk.
In this large cohort of European patients with RA, no association was seen between the short-term risk of ischemic stroke and the use of anti-TNF therapy, she said, adding that additional follow-up is needed to assess risk over time.
Dr. Low reported having no relevant financial disclosures.