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19. Tumor necrosis factor-alpha antagonists and cardiovascular disease in inflammatory bowel disease

N. Nyboe Andersen1, C. Rungoe1, M. Andersson1, P. Munkholm2, B. Pasternak1, T. Jess1, 1Statens Serum Institut, Department of Epidemiology Research, Copenhagen, 2Herlev University Hospital, Department of Gastroenterology, Copenhagen, Denmark


It is suggested that patients with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease (CVD), potentially due to systemic inflammation. Tumour necrosis factor-alpha (TNF-α) antagonists are increasingly used in the treatment of IBD, being highly effective in reducing the inflammatory burden. However, data on the potential impact of this anti-inflammatory effect on risk of CVD in IBD remains limited. We conducted a nationwide, population-based, cohort study of risk of CVD, subdivided into ischemic heart disease (IHD) and cerebrovascular event (CVE), among patients with IBD followed for up to 11 years after exposure to TNF-α antagonists.


The cohort consisted of 50,756 IBD patients of whom 3,109 had been exposed to TNF-α antagonists during 1999–2010. Diagnoses of CVD were obtained from the Danish Patient Register. Using Poisson regression and adjusting for age, calendar year, disease duration, propensity scores that included cardiovascular risk factors, and use of other IBD medications, we calculated rate ratios (RR) with 95% confidence intervals for IHD and CVE among TNF-α exposed and non-exposed.


During 386,387 person-years of follow-up, 31 TNF-α antagonist-exposed patients and 2,641 unexposed patients developed IHD, yielding a crude RR of 0.83 [95% CI: 0.58–1.18] and an unchanged adjusted RR of 0.85 [95% CI: 0.59–1.24]. For men the RRadjusted was 0.71 [95% CI: 0.41–1.26] and for women RRadjusted: 0.98 [95% CI: 0.60–1.61]. In contrast, the RRcrude for CVE (n = 15) associated with TNF-α antagonists was 1.51 [95% CI: 0.90–2.52] and RRadjusted: 1.42 [95% CI: 0.82–2.45]. The RRadjusted was 1.93 [95% CI: 0.94–3.94] in men and 0.98 [95% CI: 0.42–2.30] in women.


Our nationwide cohort study of patients with IBD found no significant associations between TNF-α antagonist-exposure and risk of IHD and CVE. Nonetheless, the point estimates indicate that there might be decreased risk of IHD and increased risk of CVE in men exposed to TNF-α antagonists. These findings need further evaluation.