Effect of Sarilumab on Atherosclerotic Disease Assessed by PET/CET in Patients With RA (SARIPET)
Status:
Not yet recruiting
Trial end date:
2021-04-30
Target enrollment:
Participant gender:
Summary
Rheumatoid arthritis (RA) is a condition associated with a high incidence of cardiovascular
disease (CV), primarily as a result of accelerated atherosclerosis . Patients with RA also
have a high prevalence of metabolic syndrome (MS) The state of chronic inflammation in RA
patients contributes to increased CV risk.
Deregulation of both genetic and serological adipocines, MS biomarkers, and biomarkers of
endothelial activation and inflammation also contributes to the increased CV risk in these
patients.
An increased incidence of abnormal carotid intima-media thickness (cIMT) values and carotid
plaques, considered surrogate markers of subclinical atherosclerotic disease, has also been
described in patients with RA.
Positron emission tomography/computed tomography (PET/CT) is a noninvasive imaging technique
useful for the evaluation of inflammation (by 18F-FDG uptake) and mineralization (by 18F-NaF
uptake) in carotid atheroma plaque.
Atherosclerosis and RA share many common inflammatory pathways, and the mechanisms that lead
to synovial inflammation are similar to those seen in atherosclerotic plaque.
Interleukin (IL)-6 is a key pro-inflammatory cytokine involved in both the pathophysiology of
RA and the development of atherosclerosis.
Sarilumab is a human monoclonal antibody against the IL-6 receptor that has been shown to be
effective in patients with RA, improving symptoms, as well as at the functional and
radiographic levels.
Treatment with IL-6 receptor inhibitors has been described to result in a modulation of lipid
metabolism, mediated by a reduction in lipoprotein (a) (Lp(a)) and an improvement in the
anti-oxidant function of high-density lipoprotein (HDL) . In this regard, Sarilumab may have
beneficial effects in RA patients on MS, which is implicated in the development of
atherosclerotic disease.
Information regarding the beneficial effect of IL-6 receptor blockade on atheroma plaque
formation and its effect at the vascular level in RA patients is scarce.