Do anti-tumour necrosis factor-α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review

Aims: Inflammatory cytokines, particularly tumour necrosis factor-alpha (TNF alpha), are thought to promote arterial disease through a variety of mechanisms leading to arteriosclerosis and atherosclerosis. We reviewed the existing evidence of the effect of anti-TNF alpha treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease. Methods: We performed a systematic review of studies examining effects of monoclonal antibodies against TNF alpha on subclinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flow-mediated dilation or forearm blood flow responses to endothelium-dependent agonists, and common carotid intima-media thickness). Results: We identified 60 studies (of 854 potential studies identified using a systematic search) in which effects of anti-TNF alpha biologics on these measures were assessed in patients receiving anti-TNF alpha therapy for a clinical indication (usually an inflammatory disease such as an inflammatory arthritis, psoriasis or inflammatory bowel disease). Of these, only 6 were randomised clinical controlled trials. Whilst many observational studies and noncontrolled studies reported positive findings, positive finding were reported in only 1 of 6 randomised clinical controlled trials. Conclusions: There is no strong evidence for an effect of anti-TNF alpha biologics on the subclinical measures of arteriosclerosis or atherosclerosis examined in this review. This does not exclude a positive effect of TNF alpha biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.