Cardiovascular safety of biologic therapies for the treatment of RA

Abstract

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Safety of biologic DMARDs in RA patients in real life: A systematic literature review and meta-analyses of biologic registers

“…But the association between anti-TNFs and fewer cardiovascular events is consistent across registers, time of publication, ages and socioeconomic groups [13,47,60]. Regarding solid cancers, we did not found excess risk under anti-TNF.…”

“…According to the Swedish Biologics Register (ARTIS), no major differences in cancer stage at diagnosis or in post-cancer survival were observed as compared to biologics-naive RA patients with cancer [34]. Only 2 studies from RABBIT and CORRONA registers reported data on cancer under non anti-TNFs treatment: no increased risk of cancer was detected with anakinra comparing to cDMARD (adjusted hazard ratio = 1.4 [0.6-3.5]) [13], with abatacept (HR = 1.55 [0.40-5.97]) and rituximab (HR = 0.42 [0.07-2.60]) comparing to methotrexate [35].…”

“…From 813 abstracts, we selected 309 publications from 36 registers. Sixteen published reviews allowed us to identify 7 other registries with no publication identified in databases (hand search) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment

“…Furthermore, acute phase reactants (APRs), typically elevated in RA, have been shown to be associated with subclinical atherosclerosis, indicated by increased carotid artery intima–media thickness (cIMT) [56] and CV morbidity and mortality in patients with RA [57]. In the general population, CRP level is an independent predictor of CV risk, particularly MI [58], while in both RA patients and healthy subjects, CRP is associated with the number of atherosclerotic plaques and cIMT [49, 59].…”

Left ventricular function in rheumatoid arthritis during anti-TNF-α treatment: a speckle tracking prospective echocardiographic study

“…Anti-TNF-α therapy has been reported to decrease cardiovascular risk in RA, with multiple reasons being attributed to this reduction: decreased systemic inflammation, corticoid-sparing effects, and increased high density lipoprotein (HDL) levels [5,6] but the exact underlying mechanism(s) have been widely debated [7].…”