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

Abstract

Aims: Inflammatory cytokines, particularly tumour necrosis factor-α (TNFα), 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-TNFα treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease. Methods:We performed a systematic review of studies examining effects of monoclonal antibodies against TNFα on subclinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flowmediated 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-TNFα biologics on these measures were assessed in patients receiving anti-TNFα 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-TNFα biologics on the subclinical measures of arteriosclerosis or atherosclerosis examined in this review.This does not exclude a positive effect of TNFα biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.

Endothelial Dysfunction in Psoriasis: An Updated Review

“…Tumor necrosis factor-α inhibitors (adalimumab, certolizumab, etanercept, or infliximab) showed a protective cardiovascular profile in multiple, mainly observational studies of psoriasis. It has been hypothesized that this action is probably mediated by their beneficial effect on endothelial cell function (66). There is at present no strong, definite evidence for a significant beneficial effect of anti-TNF-α biologics on endothelial function in psoriasis (66,67), although some promising data do exist.…”

“…It has been hypothesized that this action is probably mediated by their beneficial effect on endothelial cell function (66). There is at present no strong, definite evidence for a significant beneficial effect of anti-TNF-α biologics on endothelial function in psoriasis (66,67), although some promising data do exist. TNF-α blockade has led to improvement of vascular function assessed through resting endothelium-dependent vascular tone by low-flow-mediated constriction, yet FMD values remained unchanged (68).…”

Tumor necrosis factor α and its role in pathologies

“…Предполагали, что необходимо устранить избыток ФНО-α в организме, подавить хроническое воспаление сосудистой стенки, и победа будет достигнута. Однако эксперименты с ингибированием ФНО-α разочаровали: атерогенез усиливался [36]. Возможно, статины, аспирин, метотрексат, колхицин обладают иммуномодулирующим эффектом и оказывают антиатерогенный эффект, подавляя в какой-то степени хроническое воспаление [32].…”

Cardiometabolic Comorbidities in Patients With Psoriasis: Focusing on Risk, Biological Therapy, and Pathogenesis

“…Anti-TNF- α therapy also has a favorable effect on the improvement of arterial stiffness, measured by the gold standard aortic pulse wave velocity (aPWV), in patients with psoriatic arthritis ( Angel et al, 2010 ). Despite that a recent systematic review showed no significant effect of TNF- α inhibitors on the subclinical indicators of atherosclerosis in inflammatory diseases including psoriasis, a positive effect of TNF- α biologics on the clinical outcomes of CVDs via alternate pathways, such as primary disease remission or reduced prothrombotic tendency, cannot be ruled out ( Knowles et al, 2020 ).…”